Eosinophil-associated micro-inflammation in the gastroduodenal tract contributes to gastric hypersensitivity in a rat model of early life adversity

2020 ◽  
Author(s):  
Shaoqi Duan ◽  
Takashi Kondo ◽  
Hiroto Miwa ◽  
Yanjing Yang ◽  
Shenglan Wang ◽  
...  
Keyword(s):  
Maternal Separation ◽  
Underlying Mechanism ◽  
Eosinophil Infiltration ◽  
Sprague Dawley ◽  
Early Life Adversity ◽  
Gastric Distention ◽  
Sprague Dawley Rats ◽  
Visceromotor Response ◽  
Expression Rate ◽  
Clinical Characteristic

Gastric hypersensitivity is a major pathophysiological feature of functional dyspepsia (FD). Recent clinical studies have shown that a large number of FD patients present with gastroduodenal micro-inflammation, which may be involved in the pathophysiology of FD. However, no animal model reflecting this clinical characteristic has been established. The underlying mechanism between micro-inflammation and FD remains unknown. In this study, using a maternal separation (MS)-induced FD model, we aimed to reproduce the gastroduodenal micro-inflammation and reveal the interaction between gastroduodenal micro-inflammation and gastric hypersensitivity. The MS model was established by separating newborn Sprague Dawley rats for 2 h a day from postnatal day 1 to day 10. At 7-8 weeks of age, electromyography was used to determine the visceromotor response to gastric distention (GD) and immunohistochemistry was performed to detect distension-associated neuronal activation as well as immunohistological changes. Our results demonstrated that MS-induced FD rats underwent gastric hypersensitivity with GD at 60 and 80 mmHg, which are related to increased p-ERK1/2 expression in the dorsal horn of T9-T10 spinal cords. Eosinophils, but not mast cells, were significantly increased in the gastroduodenal tract, and the co-expression rate of CD11b and major basic protein significantly increased in MS rats. Treatment with dexamethasone reversed gastric hypersensitivity in MS-induced FD rats by inhibiting eosinophil infiltration. These findings indicated that neonatal MS stress induces eosinophil-associated gastroduodenal micro-inflammation and gastric hypersensitivity in adulthood in rats. Micro-inflammation contributes to gastric hypersensitivity; therefore, anti-inflammatory therapy may be effective in treating FD patients with gastroduodenal micro-inflammation.

scholarly journals Antiapoptosis and Antifibrosis Effects of Qishen Granules on Heart Failure Rats via Hippo Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Jian Zhang ◽  
Junjie Liu ◽  
Sheng Gao ◽  
Weili Lin ◽  
Pengrong Gao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hippo Pathway ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Regulatory Pathways ◽  
Sprague Dawley Rats ◽  
The Hippo Pathway ◽  
Related Proteins ◽  
P 53

Qishen granules (QSG) are a famous formula with cardioprotective properties to heart failure (HF). The aim of this study was to investigate the underlying mechanism of QSG on apoptosis and fibrosis in the treatment of HF. HF model was induced by left anterior descending artery ligation on Sprague-Dawley rats. Transcriptome analysis was used to investigate the regulatory pathways of QSG on HF. Interestingly, downregulated genes of QSG were significantly enriched in Hippo pathway which plays a crucial role in regulating cell apoptosis and proliferation. We found that QSG inhibited the expressions of proapoptotic key proteins P-53 and fibrosis-related proteins TGF-β1, SMAD3, and CTGF. Further, we conducted research on the key proteins in the Hippo pathway upstream of CTGF and P-53. The results showed that MST1, P-MST1, P-LATS1, and RASSF1A that exert proapoptotic function were downregulated after QSG intervention. Similarly, P-YAP and P-TAZ, mediating self-degradation and apoptosis, were both observably decreased after QSG administration. Taken together, QSG are shown to be likely to exert cardioprotective effects by inhibiting the progression of apoptosis and fibrosis through Hippo pathway.

scholarly journals Electroacupuncture Pretreatment at GB20 Exerts Antinociceptive Effects via Peripheral and Central Serotonin Mechanism in Conscious Migraine Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Liu ◽  
Pei Pei ◽  
Luo-Peng Zhao ◽  
Zheng-Yang Qu ◽  
Yu-Pu Zhu ◽  
...  
Keyword(s):  
High Performance ◽  
Antinociceptive Effect ◽  
Underlying Mechanism ◽  
Sham Acupuncture ◽  
Sprague Dawley ◽  
Grooming Behavior ◽  
Sprague Dawley Rats ◽  
Serotonin System ◽  
Antinociceptive Effects ◽  
Exploration Behavior

Background. While electroacupuncture (EA) pretreatment in migraine has been found to attenuate pain and frequencies of attacks, the underlying mechanism of its antinociceptive effect remains poorly understood. Emerging evidence suggests that the serotonin system may be involved in migraine pathophysiology.Method. Forty male Sprague-Dawley rats were randomly assigned to Control, Model, EA, and sham acupuncture (SA) groups. HomeCageScan was used to measure the effects on spontaneous nociceptive behaviors. Radioimmunoassay and high-performance liquid chromatography were used to evaluate the expression of 5-hydroxytryptamine (HT) in the plasma and three-key structure of the descending pain modulatory system.Results. Our study showed that EA pretreatment could produce a significant reduction in resting, freezing, and grooming behavior and a significant increase in exploration behavior. Furthermore, we found that the level of 5-HT in plasma was significantly increased, and it was significantly decreased in the descending pain modulatory system in Model group. The aforementioned results were significantly reversed in EA group; that is, the level of 5-HT was increased in the rostroventromedial medulla (RVM) and trigeminal nucleus caudalis (TNC) region and decreased in the plasma.Conclusion. EA pretreatment exerts antinociceptive effects in a rat model of recurrent migraine, possibly via modulation of the serotonin system.

Congenital Bilateral Vocal Cord Paralysis and the Role of Glycine

2005 ◽  
Vol 114 (6) ◽  
pp. 494-498 ◽  
Author(s):  
Robert G. Berkowitz ◽  
Qi-Jian Sun ◽  
Paul M. Pilowsky
Keyword(s):  
Vocal Cord ◽  
Vocal Cord Paralysis ◽  
Clinical Manifestations ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Bilateral Vocal Cord Paralysis ◽  
Sprague Dawley Rats ◽  
Motoneuron Activity ◽  
Made In

Objectives: We sought to modify normal laryngeal constrictor (LC) motoneuron activity to induce a pattern of aberrant LC muscle function that may serve as a model of congenital bilateral vocal cord paralysis. Methods: Single unit extracellular recordings of functionally identified LC motoneurons were made in anesthetized Sprague-Dawley rats, and the response to both intravenous and iontophoretic application of the glycine antagonist strychnine was studied. Results: The postinspiratory firing pattern of LC motoneurons became inspiratory after intravenous injection of strychnine (4 of 5 rats), but no change was recorded in response to strychnine iontophoresis (7 of 8 rats). Conclusions: Blockade of glycinergic inhibitory neurotransmission by strychnine, acting above the level of the LC motoneuron, causes LC motoneurons to fire during inspiration rather than after inspiration. This observation suggests that impaired glycine neurotransmission may be an underlying mechanism that explains the clinical manifestations of congenital bilateral vocal cord paralysis.

scholarly journals QiShenYiQi Pills Attenuates Ischemia/Reperfusion-Induced Cardiac Microvascular Hyperpermeability Implicating Src/Caveolin-1 and RhoA/ROCK/MLC Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Chun-Shui Pan ◽  
Li Yan ◽  
Se-Qi Lin ◽  
Ke He ◽  
Yuan-Chen Cui ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Chain Complex ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Microvascular Damage ◽  
Caveolin 1 ◽  
Src Inhibitor ◽  
Sprague Dawley Rats ◽  
Albumin Leakage ◽  
Cardiac Microvascular Endothelial Cells

Aims: Coronary microvascular hyperpermeability is an important contributor to ischemia or reperfusion (I/R) injury. However, the effective strategy for this insult remains limited. This study aimed to explore the protective effect of the compound Chinese medicine QiShenYiQi Pills (QSYQ) against coronary microvascular hyperpermeability after cardiac I/R with focusing on the underlying mechanism.Methods and Results: Male Sprague-Dawley rats under anesthesia were subjected to occlusion of left coronary anterior descending artery followed by reperfusion. QSYQ was administrated 90 min before ischemia initiation. Human cardiac microvascular endothelial cells (HCMECs) underwent hypoxia or reoxygenation (H/R) challenge with QSYQ administrated 1 h prior to hypoxia. QSYQ exhibited effects on attenuating microvascular damage and albumin leakage after I/R injury, showing a role in maintaining endothelial junctions, caveolae, and collagen in basement membrane (BM) of microvessels. Study using HCMECs disclosed that QSYQ protected endothelial barrier from impairment by H/R, attenuating the decline of respiratory chain complex I and ATP synthase, activation of Src/caveolin-1 and increase of RhoA/ROCK/p-MLC, MMP-9, and CTSS. PP2, a Src inhibitor, partially imitated the effect of QSYQ.Conclusions: The QSYQ was able to prevent I/R-induced cardiac microvascular hyperpermeability via a mechanism involving Src/caveolin-1 and RhoA/ROCK/MLC signaling.

Denervation inhibits early increase in Na(+)-H+ exchange after uninephrectomy but does not suppress hypertrophy

1992 ◽  
Vol 263 (2) ◽  
pp. F328-F334 ◽  
Author(s):  
M. Mackovic-Basic ◽  
R. Fan ◽  
I. Kurtz
Keyword(s):  
Atpase Activity ◽  
Renal Denervation ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Renal Hypertrophy ◽  
Kidney Weight ◽  
Luminal Membrane ◽  
Sprague Dawley Rats ◽  
Renal Sympathetic

Na(+)-H+ exchange in the rat proximal tubule luminal membrane increases approximately 30% within 15 min after the contralateral uninephrectomy. The present study was designed to test whether altered renal sympathetic nerve outflow to the remaining kidney is the underlying mechanism of increased antiport activity and whether suppression of Na(+)-H+ antiport activity by renal denervation inhibits renal hypertrophy in the remaining kidney after uninephrectomy. Sprague-Dawley rats were divided into four groups: 1) sham operated, 2) uninephrectomized, 3) uninephrectomized with prior denervation of the remaining kidney, and 4) contralateral renal denervation. Na(+)-H+ antiport activity (brush-border vesicles), Na(+)-K(+)-ATPase activity (basolateral vesicles), and kidney weight were measured days 1-7. On days 1 and 7, Na(+)-H+ antiport activity and Na(+)-K(+)-ATPase activities were significantly greater in uninephrectomized rats. Denervation of the remaining kidney before contralateral uninephrectomy prevented the stimulation of the antiporter and Na(+)-K(+)-ATPase activity, but failed to inhibit renal hypertrophy by day 7. In separate experiments, contralateral renal denervation alone without removal of the kidney stimulated the Na(+)-H+ antiporter and Na(+)-K(+)-ATPase activity. Kidney weight, however, remained unchanged. The results demonstrate a dissociation between the activation of the Na(+)-H+ antiporter and induction of renal hypertrophy in vivo.

Notoginsenoside R1 Attenuates Hypoxia and Hypercapnia-Induced Vasoconstriction in Isolated Rat Pulmonary Arterial Rings by Reducing the Expression of ERK

2014 ◽  
Vol 42 (04) ◽  
pp. 799-816 ◽  
Author(s):  
Yixiao Xu ◽  
Lina Lin ◽  
Lanlan Tang ◽  
Mengxiao Zheng ◽  
Yingchun Ma ◽  
...  
Keyword(s):  
Pulmonary Arteries ◽  
Panax Notoginseng ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Third Order ◽  
Pulmonary Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Specific Objective ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a disease of the small pulmonary arteries characterized by increased vascular resistance. Pulmonary vasoconstriction has been proven to play a pivotal role in PAH. We have previously hypothesized that Panax notoginseng saponins (PNS) might attenuate hypoxia–hypercapnia-induced pulmonary vasoconstriction. The specific objective of the present study was to investigate the role of notoginsenoside R1, a main ingredient of PNS, in this process and the possible underlying mechanism. The third order pulmonary rings from the Sprague-Dawley rats were treated with different concentrations of notoginsenoside R1 (8, 40, and 100 mg/L, respectively) both before and during the conditions of hypercapnia and hypoxia. Contractile force changes in the rings were detected and the optimal concentration (8 mg/L) was selected. Furthermore, an ERK inhibitor, U0126, was applied to the rings. In addition, pulmonary arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic conditions, and notoginsenoside R1 was administered to detect the changes induced by ERK1/2. The results revealed biphasic vasoconstriction in rings under hypoxic and hypercapnic conditions. It is hypothesized that the observed attenuation of vasoconstriction and the production of vasodilation could have been induced by notoginsenoside R1. This effect was found to be significantly reinforced by U0126 (p < 0.05 or p < 0.01). ERK expression in the PASMCs under hypoxic and hypercapnic conditions was significantly activated (p < 0.05 or p < 0.01) and the observed activation was attenuated by notoginsenoside R1 (p < 0.05 or p < 0.01). Our findings strongly support the significant role of notoginsenoside R1 in the inhibition of hypoxia–hypercapnia-induced vasoconstriction by the ERK pathway.

scholarly journals Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Duan-Yong Liu ◽  
Chun-Shui Pan ◽  
Yu-Ying Liu ◽  
Xiao-Hong Wei ◽  
Chang-Man Zhou ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Inflammatory Responses ◽  
Mucosal Injury ◽  
Underlying Mechanism ◽  
Trinitrobenzene Sulfonic Acid ◽  
Sprague Dawley ◽  
Colonic Injury ◽  
Sprague Dawley Rats ◽  
Microcirculatory Disturbances

Huang Qi Jian Zhong Pellet (HQJZ) is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg) for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day after TNBS challenge and did not recover distinctively until day 15, including an increase in macro- and microscopic scores, a colonic weight index, a decrease in colonic length, a number of functional capillaries, and blood flow. Inverted intravital microscopy and ELISA showed colonic microcirculatory disturbances and inflammatory responses after TNBS stimulation, respectively. TNBS decreased occludin, RhoA, and ROCK-I, while increasing Rac-1, PAK-1, and phosphorylated myosin light chain. In addition, ATP content and ATP5D expression in colonic mucosa decreased after TNBS challenge. Impressively, treatment with HQJZ significantly attenuated all of the alterations evoked by TNBS, promoting the recovery of colonic injury. The present study demonstrated HQJZ as a multitargeting management for colonic mucosal injury, which set in motion mechanisms involving improvement of energy metabolism.

scholarly journals Leptin Increases Blood Pressure and Markers of Endothelial Activation during Pregnancy in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hisham Saleh Ibrahim ◽  
Effat Omar ◽  
Gabrielle Ruth Anisah Froemming ◽  
Harbindar Jeet Singh
Keyword(s):  
Blood Pressure ◽  
Underlying Mechanism ◽  
Endothelial Activation ◽  
Treated Group ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Sprague Dawley ◽  
Protein Excretion ◽  
Sprague Dawley Rats ◽  
Group 1

Raised leptin levels have been reported in the placentae and serum of women with elevated blood pressure and proteinuria during pregnancy. The role of leptin in this however remains unknown. This study investigates the effect of leptin administration on systolic blood pressure (SBP) and proteinuria and serum markers of endothelial activation during pregnancy inSprague Dawley rats. From day 1 of pregnancy, 24 rats were randomised into those given either saline (group 1) or leptin at 60 or 120 μg/kg/body weight/day (groups 2 and 3 resp.). SBP was measured every 5 days and 24-h urinary protein was measured at days 0 and 20 of pregnancy. Animals were euthanised on day 20 of pregnancy, and serum was collected for estimation of E-selectin and ICAM-1. Compared to group 1, SBP during the latter part of the pregnancy was significantly higher in the leptin-treated group (P<0.01). Urinary protein excretion, serum E-selectin, and ICAM-1 were significantly higher in leptin-treated rats (P<0.05). It seems that leptin administration to normotensiveSprague Dawley ratsduring pregnancy significantly increases SBP, urinary protein excretion, and markers of endothelial activation. However, further studies are required to examine the underlying mechanism responsible for this and its relevance to preeclampsia in humans.

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