文章摘要
黄亚医,黄 婷,赵 博,汪华新,肖业达.TLR7在1型糖尿病大鼠肾缺血再灌注损伤中的作用研究[J].,2019,19(3):411-415
TLR7在1型糖尿病大鼠肾缺血再灌注损伤中的作用研究
The Effect of TLR7 on Renal Ischemia Reperfusion Injury in Type 1 Diabetic Rats
投稿时间:2018-05-05  修订日期:2018-06-03
DOI:10.13241/j.cnki.pmb.2019.03.003
中文关键词: TLR7  糖尿病  肾缺血再灌注损伤
英文关键词: TLR7  Diabetes  Renal ischemia reperfusion injury
基金项目:湖北省卫生健康委科研基金项目(WJ2019M193);湖北省自然科学基金项目(2017CFB267)
作者单位E-mail
黄亚医 武汉大学人民医院麻醉科 湖北 武汉 430060 huangyayi@126.com 
黄 婷 武汉大学人民医院麻醉科 湖北 武汉 430060  
赵 博 武汉大学人民医院麻醉科 湖北 武汉 430060  
汪华新 武汉大学人民医院麻醉科 湖北 武汉 430060  
肖业达 武汉大学人民医院麻醉科 湖北 武汉 430060  
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中文摘要:
      摘要 目的:探讨Toll样受体7(TLR7)介导的MyD88/NF-κB信号通路在1型糖尿病大鼠肾缺血再灌注损伤中的作用。方法:雄性SD大鼠随机分为3组(n=6),糖尿病假手术组(DS),糖尿病缺血再灌注组(DIR),糖尿病缺血再灌注+氯喹预处理组(DIR+CQ)。采用腹腔注射链尿佐菌素65 mg/kg建立糖尿病模型,TLR7抑制剂氯喹预处理于糖尿病模型成功后第3周0.5%氯喹40 mg/kg进行腹腔注射,连续给药7天。于第四周采用双侧肾蒂夹闭25 min,再灌注48 h建立肾缺血再灌注损伤模型。取大鼠肾脏HE染色观察大鼠病理学结果,血标本测定血尿素氮(BUN) 和血肌酐(Scr)水平,ELISA法检测白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α),TUNEL法检测细胞凋亡,Western blot检测TLR7,MyD88和NF-κB蛋白表达。结果:与DS组相比,DIR组肾小管肿胀,间质水肿,刷状缘丢失,空泡变性坏死,Paller评分升高(P<0.01)。与DIR组相比,氯喹预处理可以改善肾损伤(P=0.017);与DS组相比,DIR组BUN,Scr,IL-6,TNF-α,细胞调亡指数(Apoptosis %),TLR7,MyD88,NF-κB增高(P<0.05);与DIR组相比,DIR+CQ组BUN,Scr,IL-6,TNF-α,Apoptosis %,TLR7,MyD88,NF-κB降低(P<0.05)。结论:TLR7介导的MyD88/NF-κB信号通路参与糖尿病肾缺血再灌注损伤,氯喹通过抑制TLR7表达,阻断MyD88/NF-κB信号通路,降低炎症反应,从而减轻1型糖尿病大鼠肾缺血再灌注损伤
英文摘要:
      ABSTRACT Objective: To investigate the role of MyD88/NF-κB signaling pathway induced by TLR7 on renal ischemia reperfusion injury in Type 1 diabetic rats. Methods: The male SD rats, were randomly divided into three groups (n=6): diabetic sham group (group DS); diabetic ischemia reperfusion group (group DIR); diabetic ischemia reperfusion plus chloroquine pretreatment group (group DIR+CQ). The diabetic model was established by intraperitoneal injection of streptozotocin 65 mg/kg. Chloroquine, a TLR7 inhibitor, was pretreated by intraperitoneal injection of 0.5% chloroquine 40 mg/kg daily for 7 consecutive days at the third week after the diabetes model was successful. The renal ischemia reperfusion injury model was induced by occlusion of bilateral renal pedicle for 25 min and reperfusion for 48 h after the fourth week. The rats were sacrificed at 48h of reperfusion and the kidneys were removed for HE staining, the level of blood urea nitrogen (BUN) and blood serum creatinine (Scr), detection of interleukin - 6 (IL-6) and tumor necrosis factor α (TNF- α) by ELISA, cell apoptosis was detected by TUNEL and the expression of TLR7, MyD88 and NF-κB protein by western blotting. Results: Compared with group DS, the renal tubules were swelling, interstitial edema, the brush border was losing and the cavitation was necrosis in group DIR, the Paller score was increased(P<0.05). After chloroquine preconditioning, the degree of renal injury was obviously relieved (P=0.017), compared with group DIR. Compared with group DS, BUN, Scr, IL-6, TNF-α, Apoptosis %, TLR7, MyD88 and NF-κB were increased in group DIR (P<0.05). Compared with group DIR, BUN, Scr, IL-6, TNF-α, Apoptosis %, TLR7, MyD88 and NF-κB were decreased in group DIR+CQ (P<0.05). Conclusion: MyD88/NF-κB pathway induced by TLR7 is participated in Type 1 diabetic renal ischemia reperfusion injury. Chloroquine inhibits renal ischemia-reperfusion injury by inhibiting TLR7 expression, blocking MyD88/NF-κB signaling pathway and reducing inflammatory reaction, thereby alleviating renal ischemia-reperfusion injury in type 1 diabetic rats.
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