scholarly journals Experimental study of the effects of hypoxia simulator on osteointegration of titanium prosthesis in osteoporotic rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiangfeng Liu ◽  
Huijun Kang ◽  
Jiangfeng Lu ◽  
Yike Dai ◽  
Fei Wang

Abstract Background Poor osseointegration is the key reason for implant failure after arthroplasty,whether under osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine (DFO) can accelerate osteogenesis by activating the hypoxia signaling pathway. The purpose of this study was to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with a 3D printed titanium prosthesis in the bones of osteoporotic rats. Materials and methods Ninety female Sprague–Dawley rats were used for the experiment. Ten rats were used to confirm the successful establishment of the osteoporosis model: five rats in the sham operation group and five rats in the ovariectomy group. After ovariectomy and knee arthroplasty were performed, the remaining 80 rats were randomly divided into DFO and control groups (n = 40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction (PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF, and CD31. HIF-1a and VEGF have been shown to promote angiogenesis and bone regeneration, and CD31 is an important marker of angiogenesis. After 12 weeks, the specimens were examined by micro-computed tomography (micro-CT), biomechanics, and histopathology to evaluate osteogenesis and osseointegration. Results The results of PCR showed that the mRNA levels of VEGF and CD31 in the DFO group were significantly higher than those in the control group. The immunohistochemistry results indicated that positive cell expression of HIF-1a, VEGF, and CD31 in the DFO group was also higher. Compared with the control group, the micro-CT parameters of BMD, BV/TV, TB. N, and TB. Th were significantly higher. The maximal pull-out force and the bone-to-implant contact value were also higher. Conclusions The local administration of DFO, which is used to activate the HIF-1a signaling pathway, can promote osteogenesis and osseointegration with a prosthesis in osteoporotic bone.

2021 ◽  
Author(s):  
Jiangfeng Liu ◽  
Huijun Kang ◽  
Jiangfeng Lu ◽  
Yike Dai ◽  
Fei Wang

Abstract Purpose: Poor osseointegration is the key reason for implant failure after arthroplasty, whether in osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine(DFO) can accelerate osteogenesis by activation of the hypoxia signal pathway. The purpose of this study is to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with titanium prosthesis in the bones of osteoporotic rats.Materials and Methods: 90 female sprague-dawley rats were used for the experiment. Ovariectomy and knee arthroplasty were performed. Then, the rats were randomly divided into DFO and control group(n=40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction(PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF and CD31. After 12 weeks, the specimens were examined by micro CT, biomechanics and histopathology to evaluate osteogenesis and osseointegration.Results: The results of PCR showed mRNA levels of VEGF and CD31 in DFO group were significantly higher than those in control group. The immunohistochemistry results indicated positive cell expressions of HIF-1a, VEGF and CD31 in DFO group were also higher. Compared to control group, the microCT parameters of BMD, BV/TV, TB.N, TB.Th were significantly higher. The maximal pull-out force and the bone-to-implant contact (BIC) value were also higher . Conclusions: The local administration of DFO which is used to activate HIF-1a signaling pathway can promote osteogenesis and osseointegration with the prosthesis in osteoporotic bone.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shao-cheng Lyu ◽  
Jing Wang ◽  
Wen-li Xu ◽  
Han-xuan Wang ◽  
Fei Pan ◽  
...  

Background: The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model.Methods: The biliary obstruction model of Sprague Dawley (SD) rats was established in advance, and 54 rats were divided into nine groups randomly (sham operation group, anisodamine group, neostigmine group, combination group, and control group). Anisodamine (25 mg/kg) and neostigmine (50 μg/kg) were injected to the abdominal cavity separately or simultaneously for 1 week since the first day after surgery according to their allocated intervention, while the same amount of saline (0.5 ml) was injected intraperitoneally in the control group. Indexes including body weight, the diameter of the common bile duct, liver function, inflammatory indexes, and the condition of scar formation in different groups at certain time were evaluated in our study.Results: Recovery of liver function (ALT, AST, TB, DB, and GGT) and systematic inflammation indexes (CRP, TNF-α, and IL-1β) in the combination group was prior to that in the control group (p < 0.05), while no statistical difference in the serum level of IL-10 was observed among groups. Rats in the combination group represented a wider anastomotic diameter and lower expression of α-SMA and TGF-β1 at anastomotic stoma compared to the control group (p < 0.05). Histopathological staining showed slighter proliferation of collagen and smooth muscle fibers in rats’ bile duct wall and less local scar formation at anastomotic stoma compared to the control group.Conclusion: The combination of anisodamine and neostigmine can alleviate local and systemic inflammatory response, promote the recovery of liver function, and reduce scar formation in rats after the RCJS procedure.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Xueqin Zhang ◽  
Jing Fang ◽  
Zhiqiang Chen ◽  
Bingwu Zhao ◽  
Su Wu ◽  
...  

As renal fibrosis significantly contributes to various kinds of chronic kidney diseases, this study aimed to investigate the renal protective effects of Qingshen Buyang Formula against renal fibrosis on 5/6 nephrectomized rats, and its underlying mechanisms were explored. A total of 24 male Sprague-Dawley rats were randomly divided into sham operation group (Sham group), 5/6 nephrectomy group (5/6Nx group), and Qingshen Buyang Formula treatment group (QBF group). The intervention was intragastric administration for 12 weeks. In the end, the blood samples were collected to test renal functional parameters, urine proteins were measured, and the left kidneys were removed for histological studies, as well as mRNA and protein expression analysis. The results showed that Qingshen Buyang Formula significantly decreased BUN, Scr, and proteinuria in 5/6Nx rats. Meanwhile, it ameliorated the kidney injury and fibrosis, exemplified by the depressed expression of collagen I and fibronectin (FN), which are the main components of ECM. Furthermore, the process of EMT inhibited the Wnt/β-catenin signaling pathway related genes, such as Wnt4, TCF4, β-catenin, and p-GSK3β. Collectively, the Qingshen Buyang Formula can improve renal function and attenuate renal fibrosis, and its underlying mechanisms may be related with inhibiting EMT and Wnt/β-catenin signaling pathway.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae-Young Kim ◽  
Hyo-Won Jang ◽  
Jung-In Kim ◽  
In-Ho Cha

AbstractThe purpose of this study was to investigate the effect of administering intermittent parathyroid hormone (iPTH) before tooth extraction versus after tooth extraction on the risk of developing MRONJ in experimental animal model. Twenty-five ovariectomized rats received 6 weeks of bisphosphonate therapy. They were classified into 3 groups, based on the timing of the medication, as Control, Pre-PTH and Post-PTH groups. For Control group, normal saline was administered before and after tooth extraction. iPTH was administered during 4 weeks before tooth extraction for Pre-PTH group and after tooth extraction for Post-PTH group. The animals were euthanized 8 weeks after tooth extraction. Macroscopic, histological, micro-computed tomography (micro-CT), and histomorphometric examinations were conducted. The incidences of impaired healing were 11.11% both in Pre-PTH and Post-PTH groups, which was lower than the Control group (42.86%). Bone healing in the extraction socket, based on micro-CT and histomorphometry evaluations, was best in Post-PTH and worst in Control group. The Pre-PTH group showed moderate healing pattern. Despite of limitations in this study, the authors identified Pre-PTH group seems to have positive effect on extraction socket healing. With regard to timing, administering iPTH after tooth extraction was superior to applying it before tooth extraction.


2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094379
Author(s):  
Yanshan Li ◽  
Yunxiuxiu Xu ◽  
Ruomei Wang ◽  
Wenxin Li ◽  
Wenguang He ◽  
...  

Objective To investigate whether the Notch–Hif-1α signaling pathway is involved in liver regeneration. Methods Rats were divided into two groups and treated with daily intraperitoneal injections of saline (control) or the gamma-secretase inhibitor, Fli-06, for 2 days. Two-thirds of the rat livers were resected and rats were later euthanized at specific time points post-resection to analyze the remnant livers. Each group's liver/body weight ratio was calculated, and immunostaining and western blotting were used to determine the cell proliferation marker, PCNA and Ki-67 expression. Real-time PCR and western blotting were used to compare the mRNA expression of Notch homolog-1 ( Notch1), hairy and enhancer of split-1 ( Hes1), and vascular endothelial growth factor ( Vegf), and the protein expression of NICD and HIF-1α, respectively. Results The liver/body weight ratios and number of Ki-67- and PCNA-positive cells were significantly lower in the experimental group than the control group, indicating lower levels of liver regeneration following the disruption of Notch signaling by Fli-06. The Hes1 and Vegf mRNA levels and NICD and HIF-1α protein expression levels were all down-regulated by Fli-06 treatment. Conclusion Notch–Hif-α signaling pathway activation plays an important role in liver regeneration, where it may contribute toward liver cell proliferation.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Zhi-gao Sun ◽  
Ya-zhuo Hu ◽  
Yu-guo Wang ◽  
Jian Feng ◽  
Yong-qi Dou

BuPiHeWei (BPHW) decoction, a classic Traditional Chinese Medicinal (TCM) prescription, has been widely used in clinical practice to relieve digestive symptoms caused by chemotherapy, such as diarrhea and vomiting. The present study aimed to investigate whether BPHW decoction exerted a protective role in the 5-Fu-induced intestinal mucosal injury in the rats by regulating the mechanisms of TLR-4/NF-κB signaling pathway. There were 35 Sprague Dawley rats randomly divided into four groups: normal control group, 5-Fu group, 5-Fu + BPHW decoction group (10.5 g/kg, for five continuous days), and 5-Fu + Bacillus licheniformis capsule group (0.2 g/kg, for five continuous days). Animal models were established by intraperitoneal injection of 5-Fu (30 mg/Kg, for five consecutive days). At the end of the treatment period, body weight, diarrhea score, and histological examination were examined. Furthermore, the expression of TLR-4/NF-κB pathway was detected to reveal its mechanism. The results showed that BPHW decoction effectively reduced diarrhea score and increased body weight and height of villi after 5-Fu chemotherapy. In addition, BPHW decoction could significantly inhibit the expression of TLR-4, NF-κB, and inflammatory factors (including TNF-α, IL-1β, and IL-6) in the intestine, and the efficacy was significantly higher than that of Bacillus licheniformis capsule. In summary, BPHW decoction might be considered an effective drug to alleviate intestinal mucosal injury in the rats induced by 5-Fu.


2019 ◽  
Vol 97 (6) ◽  
pp. 702-708 ◽  
Author(s):  
Ting Wang ◽  
Yu-Mei Duan ◽  
Qiao Fu ◽  
Tao Liu ◽  
Jin-Cheng Yu ◽  
...  

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt–β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague–Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood–brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of β-catenin and downstream proteins while suppressing the expression of GSK-3β. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt–β-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.


1986 ◽  
Vol 251 (5) ◽  
pp. E563-E568
Author(s):  
S. Amr ◽  
S. S. Lippman ◽  
B. D. Weintraub

We investigated the function of thyrotrophs in rat pituitaries that were transplanted under the renal capsule of 3-wk-old male Sprague-Dawley rats, which were either intact or hypophysectomized. Groups of 12 animals were implanted with osmotic minipumps that delivered a constant infusion of either thyrotropin-releasing hormone (TRH; 1 mg X kg-1 X day-1) or normal saline for 1 wk. In hypophysectomized rats, TRH infusion led to the appearance of substantial amounts of biologically active serum TSH and prevented the hypothyroidism that occurred in the control group. However, TRH did not change the transplant contents of DNA, immunoactive TSH, and mRNA levels for TSH subunits. Comparison of sellar and renal pituitary tissues, obtained from intact rats after 1 wk of either saline or TRH infusion, showed that removal of the pituitary from hypothalamic influence resulted in a 90% depletion of the thyrotroph TSH content. TRH infusion depleted only 63% of the TSH content of sellar thyrotrophs. The mRNA levels for TSH beta-subunit were similar in sellar and transplanted pituitaries and did not significantly change after TRH infusion. When immunocytochemically stained using rat TSH antiserum, the thyrotrophs in pituitary transplants were morphologically and numerically indistinguishable from the thyrotrophs in sellar pituitaries, in the presence or absence of TRH. These data indicate that in transplanted pituitary, for up to 1 wk of a constant infusion, TRH does not significantly affect either the number of thyrotrophs or their ability to synthesize TSH subunit mRNA. However, it is required to maintain released TSH in circulation, since TSH levels were low in the absence of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)


2017 ◽  
Vol 35 (3) ◽  
pp. 208-214 ◽  
Author(s):  
Shulan Ma ◽  
Dongju Li ◽  
Yi Feng ◽  
Jianwei Jiang ◽  
Bo Shen

Aim To observe the effects of electroacupuncture (EA) on uterine morphology and expression of oestrogen receptor (ER) α and β in ovariectomised (OVX) rats. Methods Thirty female Sprague-Dawley rats with regular 4-day oestrus cycles were divided into a sham operation group (Control, n=10) and two OVX groups that remained untreated (OVX group, n=10) or received EA treatment (OVX+EA group, n=10). In the latter group, EA was applied at CV4, CV3, SP6 and bilateral Zigong (30 min per day) for 3 days. The effects of EA on uterine morphology were observed by H&E staining. Quantitative real-time reverse transcription-PCR (qRT-PCR) and Western blotting were used to measure ERα and ERβ mRNA and protein expression, respectively. Results Relative to the (untreated) OVX group, EA treatment significantly increased the uterine wet weight to body weight (UWW/BW) ratio (0.47±0.04 vs 0.31±0.03 g/kg, p=0.04), and myometrial thickness (109.39±10.71 vs 60.81±8.1 μm, p=0.016) of OVX rats. Similarly, the total number of endometrial glands per cross section and endometrial thickness in the OVX +EA group was significantly increased compared to the (untreated) OVX group. EA treatment also increased protein (but not mRNA) expression of both ERα and ERβ in the uteri of OVX rats. Conclusions This study has demonstrated that EA treatment decreases uterine atrophy in OVX rats. This unique effect of EA on the uterus may be due to upregulation of serum levels of E2 and differential regulation of sex steroid receptors ERα and ERβ.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Takahiro Naka ◽  
Satoshi Yokose

This study evaluated the application of laser-induced bone therapy (LIBT) to reduce implant healing time in rat tibia. Twenty 10-week-old female Sprague-Dawlay rats were used. The rats received laser irradiation (laser group) or sham operation (control group) on either side of the tibia. Five days after invasion, titanium implants were inserted in proximal tibia. Five, 10, and 20 days after implant placement, tibiae were collected. After taking micro-CT and performing a torque test, the tibiae were decalcified and 8-μm-thick sections were prepared. Specimens were stained with hematoxylin and eosin.Results. Micro-CT images, removal torque values, and histomorphometric analysis data demonstrated a significantly accelerated bone formation in the laser group earlier in the healing process.Conclusion. The use of laser irradiation was effective in promoting bone formation and acquiring osseointegration of titanium implants inserted in rat tibia. LIBT may be suitable for use in implant therapy.


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