Berberine Reduces Renal Cell Pyroptosis in Golden Hamsters with Diabetic Nephropathy through the Nrf2-NLRP3-Caspase-1-GSDMD Pathway

Objective. To observe the effect of berberine (BBR) on kidney cell pyroptosis in golden hamsters with diabetic nephropathy (DN) and to explore the molecular mechanism of its renal protection. Methods. Fifty clean-grade male golden hamsters were randomly divided into a control group (10) and a model building group (40). The DN model was established by high-sugar and high-fat feeding and injection of a small amount of STZ. After successful establishment of the model, they were randomly divided into a model group, western medicine group, and berberine high- and low-dose groups. The western medicine group was given irbesartan 13.5 mg/kg, and the berberine high- and low-dose groups were given BBR 200 mg/kg and 100 mg/kg, respectively, for 8 consecutive weeks. An automatic biochemical analyser was used to measure blood glucose, blood lipids, kidney function, MDA, and other indicators; radioimmunoassay was used to assess serum insulin; enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1β, IL-6, IL-18, TNF-α; HE, PAS, and Masson staining were used to observe kidney pathological tissue morphology; western blot and real-time fluorescent quantitative PCR were used to assess protein and mRNA expression of molecules, such as Nrf2, NLRP3, Caspase-1, and GSDMD; and TUNEL staining was used to detect DNA damage. SPSS statistical software was used for the data analysis. Results. The kidney tissues of golden hamsters in the control group were normal; Nrf2 was highly expressed, serum MDA level was low, NLRP3 expression in kidney tissue was not obvious, Caspase-1 and GSDMD were weakly expressed, and only a few TUNEL-positive cells were observed. Compared with the control group, the golden hamsters in the model group had obvious renal pathological damage; blood glucose, blood lipids, renal function-related indexes, insulin, and inflammatory factors IL-1β, IL-6, IL-18, and TNF-α were increased ( P < 0.05 ); NLRP3, Caspase-1, and GSDMD expression was increased; Nrf2 expression was decreased; MDA level was increased ( P < 0.05 ); and the number of TUNEL-positive cells was increased. Compared with the model group, the pathological morphology of the kidney tissue of golden hamsters in the three treatment groups was significantly improved; blood glucose, blood lipids, renal function, and the expression of inflammatory factors IL-1β and IL-6 were reduced ( P < 0.05 ); NLRP3, Caspase-1, GSDMD, and other molecular proteins and mRNA expression were decreased; Nrf2 expression was increased; MDA level was decreased ( P < 0.05 ); and the number of TUNEL-positive cells was decreased. Conclusion. DN golden hamster kidney NLRP3-Caspase-1-GSDMD signalling was enhanced. BBR can reduce oxidative stress damage by regulating antioxidative Nrf2 and then regulating NLRP3-Caspase-1-GSDMD signalling to inhibit pyroptosis, antagonizing DN inflammation-induced damage.

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The Correlation Analysis Between the Blood Lipids, Glycosylated Protein Level and Inflammatory Factors of Pregnant Women with GDM During Pregnancy and the Weight of Newborn

10.21203/rs.3.rs-896430/v1 ◽

2021 ◽

Author(s):

Changhua Hu ◽

Lirong Wu ◽

Juan Fang

Keyword(s):

Blood Glucose ◽

Pregnant Women ◽

Research Group ◽

Blood Lipids ◽

Fasting Blood Glucose ◽

Blood Lipid ◽

Adverse Outcomes ◽

Inflammatory Factors ◽

Control Group ◽

Inflammatory Factor

Abstract The study was carried to explore the correlation between blood lipids, blood glucose levels, inflammatory factor and weight of newborn, to provide reference for control of blood glucose in pregnant women with gestational diabetes mellitus (GDM) and early screening of macrosomia. Fifty pregnant women (give birth to newborn) with GDM were selected as research group, and 55 normal pregnant women (give birth to newborn) as control group. Blood lipid levels of TC, TG, HDL-C, LDL-C, the fasting blood glucose (FPG), HbAlc, glycosylated albumin (GA), and expression of inflammatory factor TLR4 of pregnant women in the two groups were monitored. The levels of TG, FPG, HbA1c and GA in pregnant women, the levels of TLR4 in cord blood of newborn, the relative expression of TLR4 protein and TLR4mRNA in the placenta were higher than in control group, and level of HDL-C was lower than the control group. The levels of TC and LDL-C of pregnant women were higher than in control group. Weight of newborn was positively correlated with these all except HDL-C levels (negatively correlated) and no correlation was found with TC and LDL-C. The weight of newborn and incidence of macrosomia in research group were higher compared to control group, and scores of newborns at 1 min and 5 min were lower compared to control group. The results revealed that strengthening the detection of blood lipid and blood glucose during pregnancy can prevent adverse outcomes such as giant babies and improve the quality of birth.

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Effect of Massage on the TLR4 Signalling Pathway in Rats with Neuropathic Pain

Pain Research and Management ◽

10.1155/2020/8309745 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Qian Wang ◽

Jing Lin ◽

Peng Yang ◽

Yingye Liang ◽

Dongming Lu ◽

...

Keyword(s):

Neuropathic Pain ◽

Spinal Nerve ◽

Signalling Pathway ◽

Inflammatory Factors ◽

Control Group ◽

Group Model ◽

Model Group ◽

Expression Levels ◽

Tnf Α ◽

Massage Group

This study set out to investigate the effect of massage on the Toll-like receptor 4 (TLR4) signalling pathway in the dorsal root ganglia of rats that had undergone spinal nerve ligation (SNL), with the hypothesis that massage could be used as an analgesic. Forty female SD rats were randomly divided into 5 groups: the control group, sham-operated group, model group, sham massage group, and massage group. There were 8 rats in each group. SNL rat models were established in the model group, sham massage group, and massage group. Rats in the sham-operated group underwent surgery to expose the vertebral nerves, but no further procedures were performed. The control group consisted of intact animals. The rats in the massage group underwent massage using a massage simulation machine once a day for 14 d in succession; the hind limbs of the rats in the sham massage group were gently touched with a cloth bag once a day for 14 continuous days. The rats in the control group, the sham-operated group, and the model group did not receive any intervention and were observed for 14 d. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) of rats in each group were detected 1 d before modelling and at 1, 3, 7, and 14 d after modelling. Fourteen days after modelling, the expression levels of TLR4, IRAK1, TRAF6, TNF-α, and IL-6 were detected in all rats. The PWTL and PWMT of SNL rats were decreased, while these parameters were elevated after massage. SNL rats showed higher levels of TLR4, IRAK1, TRAF6, IL-6, and TNF-α, and massage effectively lowered the expression levels of these molecules. Inhibiting activation of the TLR4 signalling pathway, which can reduce the release of inflammatory factors, may be one mechanism by which massage treats neuropathic pain.

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Effect of Curculigo orchioides on Reflux Esophagitis by Suppressing Proinflammatory Cytokines

The American Journal of Chinese Medicine ◽

10.1142/s0192415x12500929 ◽

2012 ◽

Vol 40 (06) ◽

pp. 1241-1255 ◽

Cited By ~ 9

Author(s):

Sae-Kang Ku ◽

Jae-Soo Kim ◽

Young-Bae Seo ◽

Yong-Ung Kim ◽

Seung-Lark Hwang ◽

...

Keyword(s):

Reflux Esophagitis ◽

Group Treatment ◽

Control Group ◽

Esophageal Mucosa ◽

Dependent Manner ◽

Protective Effects ◽

Model Group ◽

Curculigo Orchioides ◽

Intact Group ◽

Tnf Α

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

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Aerobic Exercise Inhibits CUMS-Depressed Mice Hippocampal Inflammatory Response via Activating Hippocampal miR-223/TLR4/MyD88-NF-κB Pathway

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17082676 ◽

2020 ◽

Vol 17 (8) ◽

pp. 2676 ◽

Cited By ~ 1

Author(s):

Honglin Qu ◽

Ruilian Liu ◽

Jiaqin Chen ◽

Lan Zheng ◽

Rui Chen

Keyword(s):

Inflammatory Response ◽

Aerobic Exercise ◽

Exercise Group ◽

Inflammatory Factors ◽

Control Group ◽

Mild Stress ◽

Hippocampal Function ◽

Model Group ◽

Mice Model ◽

Protein Levels

Objective: To investigate the role of aerobic exercise in inhibiting chronic unpredictable mild stress (CUMS) depressed mice hippocampal inflammatory response and its potential mechanisms. Methods: Fifty-four male eight-week-old C57BL/6 mice were divided as control group (CG) (18 mice) and model group (36 mice). Model group mice were treated with 13 chronic stimulating factors for 28 days to set up the CUMS depression model. Neurobehavioral assessment was performed after modeling. The mice in the model group were randomly divided into the control model group (MG) and the aerobic exercise group (EG), with 18mice in each group. The EG group carried out the adaptive training of the running platform: 10 m/min, 0° slope, and increased by 10 minutes per day for 6 days. The formal training was carried for 8 weeks with 10 m/min speed, 0° slope, 60 min/d, 6 d/Week. After the training, a neurobehavioral assessment was performed, and hippocampus IL-1β and IL-10 protein levels were detected by ELISA. RT–PCR was used to detect the expression of miR-223 and TLR4, MyD88, and NF-κB in the hippocampus. Western blot was used to detect the expression of TLR4 and phosphorylated NF-κBp65 protein in the hippocampus. Results: The hippocampus function of CUMS depression model mice was impaired. The forced swimming and forced tail suspension time were significantly prolonged, and inflammatory factors IL-1β were significantly increased in the hippocampus. Aerobic exercise significantly improves CUMS-depressed mice hippocampal function, effectively reducing depressive behavior and IL-1β levels, and increasing IL-10 levels. Besides, aerobic exercise significantly upregulates the expression level of miR-223 and inhibits the high expression of TLR4, MyD88, and NF-κB. Conclusion: Aerobic exercise significantly increases the CUMS-depressed mice hippocampus expression of miR-223, and inhibits the downstream TLR4/MyD88-NF-κB signaling pathway and the hippocampal inflammatory response, which contributes to the improvement of the hippocampal function.

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Fasudil ameliorated liposaccharide-induced acute kidney injury in mice by inhibiting NLRP3

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i10.7 ◽

2021 ◽

Vol 20 (10) ◽

pp. 2055-2062

Author(s):

Xueqian Li ◽

Chengzhi Zhao

Keyword(s):

Acute Kidney Injury ◽

Treatment Group ◽

Cell Growth ◽

Mesangial Cells ◽

Kidney Injury ◽

Inflammatory Factors ◽

Control Group ◽

Model Group ◽

Blank Control Group ◽

Tissue Homogenates

Purpose: To determine the influence of fasudil on LPS-mediated acute kidney injury (AKI) in mice.Methods: Healthy C57 mice (n = 140) of largely similar weight were used in this study. They were assigned to a treatment group (n = 40), a model group (n = 50), and a blank control group (n = 50). Mice in treatment and model groups were injected with lipopolysaccharide (LPS). In the treatment group, each mouse was injected intravenously with fasudil daily before the establishment of the mouse model of AKI. All mice were sacrificed 6 h after establishing the AKI model. Portions of the kidney from mice were used for preparation of tissue homogenates, while the remaining portions were subjected to primary culture. Transformed C3H Mouse Kidney-1 (TCMK1) and mesangial cells from mouse glomeruli (SV40-MES-13) cells were used for assays of cell growth and apoptosis. Blood samples were alsocollected from the mice. Thereafter, the levels of blood urea nitrogen (BUN) and creatinine (Cr) in kidney homogenates of the three groups were determined. Moreover, levels of NLRP3, nuclear factor kappa-B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in the homogenates and blood were assayed. Cell growth and apoptosis were also measured.Results: The treatment group and model group showed higher levels of BUN and Cr than the control group, with a higher level observed in model mice than in the treatment mice. There were significantly higher relative levels of NF-κB, NLRP3 and TLR4 in treatment and model groups than in controls, with a higher level observed in model mice than in treatment mice. There were significantly higher concentrations of inflammatory factors in treatment and model mice groups than in control mice, with higher levels observed in model mice than in treatment mice. The TCMK1 and SV40-MES-13 cells in the two groups showed slower cell growth and stronger apoptosis than those in control group (p < 0.05).Conclusion: Fasudil relieved LPS-mediated AKI in mice by suppressing TLR4/NF-κB signal pathway and lowering NLRP3. Thus, fasudil has potential as a new adjunctive agent for the treatment of AKI.

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Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats

Medicines ◽

10.3390/medicines5030106 ◽

2018 ◽

Vol 5 (3) ◽

pp. 106 ◽

Cited By ~ 4

Author(s):

Yuanjun Deng ◽

Kairui Tang ◽

Runsen Chen ◽

Yajie Liu ◽

Huan Nie ◽

...

Keyword(s):

Signaling Pathway ◽

P38 Mapk ◽

Low Dose ◽

Serum Levels ◽

Inflammatory Factors ◽

Enzyme Linked Immunosorbent Assay ◽

High Dose ◽

Model Group ◽

Necrosis Factor Alpha ◽

Tnf Α

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

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Preoperative pain aggravates postoperative cognitive deficits and hippocampal neuroinflammation in rats

10.21203/rs.2.17941/v1 ◽

2019 ◽

Author(s):

Xiang Gao ◽

Xian Ding ◽

Huan Yi ◽

Chuan-tao Lin ◽

Yu-ping Wang ◽

...

Keyword(s):

Cognitive Function ◽

Inflammatory Factors ◽

Control Group ◽

Gamma Aminobutyric Acid ◽

Sprague Dawley ◽

Preoperative Pain ◽

Pain Model ◽

Simple Operation ◽

Tnf Α ◽

Operation Group

Abstract Background Perioperative neurocognitive disorder (PND) is the progressive deterioration of cognitive function after surgery. The purpose of this study was to observe the effect of preoperative pain on inflammatory factors and neuronal apoptosis in the hippocampus of rats. Methods 36 adult male Sprague-Dawley rats were randomly divided into 4 groups: the control group, the pain group, the pain+operation group, and the operation group. 6 days before the surgery, the rats received cognitive training, and the cognitive evaluation was carried out on the1, 3 and 7th days after the surgery. The rats were killed on the first, third and seventh days after the surgery (n = 3 rats/day). The cognitive function of rats was evaluated by the Morris Water Maze (MWM), and the expression levels of the pro-inflammatory cytokines interleukin 6(IL-6), Interleukin 1β(IL-1β)and Tumor Necrosis Factor-α(TNF-α), Acetylcholine(Ach)and Cyclic Adenosine monophosphate(cAMP), protein kinase A(PKA)and gamma-aminobutyric acid type A receptors(GABAA) in the hippocampus were measured on the 1st, 3rd and 7th days after the operation. Results Our results showed that the pain model rats exhibited impaired behavior on the first day (P< 0.001), and this lasted until the 7th day after the operation (P≤0.002 and P≤0. 001, respectively). Preoperative pain model rats showed a higher level of apoptosis than that shown by the simple operation rats. On the 1st, 3rd and 7th days after the operation, the protein content of IL-1β, IL-6 and TNF-α in the pain operation group was increased compared to that in the simple operation group (P<0.001). ACh, cAMP, PKA and GABAA expression in the hippocampus was decreased after operation in the preoperative pain model rats. Conclusion Preoperative pain is a key risk factor for the development of PND. The ACh-PKA-GABAA signaling pathway plays a key role in the acetylcholine pathway.

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Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

10.21203/rs.3.rs-101537/v1 ◽

2020 ◽

Author(s):

Wenjun Shi ◽

Fei Yang ◽

Liting Wang ◽

Nankun Qin ◽

Chengxiang Wang ◽

...

Keyword(s):

Male Rats ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

High Dose ◽

Intragastric Administration ◽

Group Model ◽

Model Group ◽

Tnf Α ◽

Plantaginis Semen ◽

Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

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Serum apolipoprotein A-1 is related to inflammatory factors in the acute phase of gout

10.21203/rs.3.rs-80620/v1 ◽

2020 ◽

Author(s):

Baoyu Zhang ◽

Yuan Wang ◽

Xiaoxia Jia ◽

Lin Mu ◽

Xiaobo Wang

Keyword(s):

Uric Acid ◽

Blood Glucose ◽

Acid Level ◽

Serum Uric Acid Level ◽

Blood Lipid ◽

Inflammatory Factors ◽

Control Group ◽

Apolipoprotein A ◽

Increase Blood Glucose ◽

Liver And Kidney

Abstract BACKGROUNDTo observe the correlation between serum apolipoprotein A-1(apoA-1) and inflammatory factors in patients with gouty arthritis. METHODSFrom February to September 2020, 97 patients with gout (gout group) and 70 healthy controls (control group) were selected as the study subjects，who were admitted to the outpatient department of Beijing lu he hospital affiliated to capital medical university.97 patients in the gout group were in the acute phase. Serum concentrations of apoA-1, NLRP3 inflammasome （NACHT-LRR-PYD protein 3,NLRP3), interleukin-1 (IL-1) and interleukin-9 (IL-9) were detected. The correlation of serum apoA-1 concentration, gout related inflammatory factors (NLRP3, IL-1 beta, IL-9) and other clinical and laboratory indicators was analyzed. RESULTSThe serum apoA-1 concentration in the gout group was lower than that in the control group (P<0.05). With the increase of serum uric acid level, serum apoA-1 concentration decreased（R2=-0.3160，P<0.05）. Multiple linear analyses were performed to increase blood glucose, blood lipid, liver and kidney, etc, and the correlation remained（OR=-3.36，P<0.05）. With the increase of serum IL-1 beta concentration, serum apoA-1 concentration decreased（R2=-0.3993，P<0.05）. Multiple linear analyses were performed to increase blood glucose, blood lipid, liver and kidney, etc., and the correlation remained（OR=-2.95，P<0.05）. CONCLUSIONSIn the acute stage of gout, as the serum uric acid level increases, the serum IL-1β concentration increases and the apoA-1 concentration gradually decreases, which may indicate that apoA-1 participates in the inflammatory response of gout to a certain extent.

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Innate inflammatory gene expression profiling in potential brain-dead donors: detailed investigation of the effect of common corticosteroid therapy

Innate Immunity ◽

10.1177/1753425917709508 ◽

2017 ◽

Vol 23 (5) ◽

pp. 440-448 ◽

Cited By ~ 3

Author(s):

Reza Gholamnezhadjafari ◽

Nader Tajik ◽

Reza Falak ◽

Reza Aflatoonian ◽

Sanaz Dehghan ◽

...

Keyword(s):

Gene Expression ◽

Flow Cytometry ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Inflammatory Factors ◽

Control Group ◽

Organ Donors ◽

Complement Components ◽

Tnf Α ◽

Brain Dead

Our study aimed to assess the influence of common methylprednisolone therapy on innate inflammatory factors in potential brain-dead organ donors (BDDs). The study groups consisted of 50 potential BDDs who received 15 mg/kg/d methylprednisolone and 25 live organ donors (LDs) as control group. Innate immunity gene expression profiling was performed by RT-PCR array. Soluble serum cytokines and chemokines, complement components, heat shock protein 70 (HSP70) and high mobility group box-1 (HMGB1) were measured by ELISA. Surface expression of TLR2 and TLR4 were determined using flow cytometry. Gene expression profiling revealed up-regulation of TLRs 1, 2, 4, 5, 6, 7 and 8, MYD88, NF-κB, NF-κB1A, IRAK1, STAT3, JAK2, TNF-α, IL-1β, CD86 and CD14 in the BDD group. Remarkably, the serum levels of C-reactive protein and HSP70 were considerably higher in the BDD group. In addition, serum amounts of IL-1β, IL-6, TNF-α, HMGB1, HSP70, C3a and C5a, but not IL-8, sCD86 or monocyte chemoattractant protein-1, were significantly increased in the BDD group. Significant differences were observed in flow cytometry analysis of TLR2 and TLR4 between the two groups. In summary, common methylprednisolone therapy in BDDs did not adequately reduce systemic inflammation, which could be due to inadequate doses or inefficient impact on other inflammatory-inducing pathways, for example oxidative stress or production of damage-associated molecules.

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