[关键词]
[摘要]
目的 研究注射用血栓通(冻干)(XST)减轻糖尿病大鼠海马神经损伤的作用。方法 ip链脲佐菌素(STZ)制备糖尿病大鼠模型,随机分为模型组和XST(50 mg/kg)组,每组10只,另随机取10只SD大鼠为对照组。ip给药,每天给药1次,于屏障环境中连续给药60 d,对照组和模型组大鼠ip等量生理盐水。常规HE染色观察大鼠海马CA1区细胞的形态;采用实时荧光定量PCR(qRT-PCR)技术对海马Bax、Bcl-2、Bcl-xl、脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)、神经突触素(Syn)mRNA水平进行检测;采用Western blotting法对3种紧密连接蛋白——海马闭锁小带蛋白1(ZO-1)、咬合蛋白(Occludin)、封闭蛋白5(Claudin-5)和BDNF蛋白表达水平进行检测。结果 与模型组比较,XST减轻糖尿病引起的海马神经细胞形态改变,显著增加细胞数目(P<0.05) ;显著升高抑凋亡基因Bcl-2、Bcl-xlmRNA的表达,降低促凋亡基因Bax mRNA的表达(P<0.05) ;XST组3种紧密连接蛋白的表达量均不同程度的升高,其中Occludin、Claudin-5差异有统计学意义(P<0.05、0.01);XST组GDNF、BDNF mRNA表达、BDNF蛋白表达均显著升高(P<0.05)。结论 XST可以减轻糖尿病大鼠海马神经损伤,其机制可能与提高紧密连接蛋白及神经营养因子表达有关。
[Key word]
[Abstract]
Objective To study the protective effect of Xueshuantong Injection (XST) on hippocampus nerve injury in diabetic rats. Methods Streptozotocin (STZ) was used to prepare diabetic rat models. Diabetic rat models were randomly divided into model group and XST (50 mg/kg) group. Another 10 SD rats were randomly selected as control group. XST was ip administration, once a day, in the barrier environment for 60 days. Rats in control group and model group were given the same amount of normal saline. Hematoxylin-eosin staining was used to observe the morphology of CA1 cells in the hippocampus of rats. Western blotting and qRTPCR were used to detect the expression of apoptose-related genes, tight-junction proteins and neurotrophic factors. Results Compared with model group, XST reduced the morphological changes of hippocampal nerve cells induced by diabetes mellitus and significantly increased the cell number (P<0.05). The expression of anti-apoptotic genes Bcl-2 and Bcl-XL mRNA was significantly increased, and the expression of pro-apoptotic gene Bax mRNA was decreased (P<0.05). The expression levels of Occludin and Claudin-5 in XST group increased to varying degrees, and the differences were statistically significant (P<0.05, 0.01). The mRNA expression of GDNF, BDNF and BDNF protein in XST group were significantly increased (P<0.05). Conclusion XST could reduce the injury of hippocampus nerve in diabetic rats, and its mechanism may be related to the increased expression of tight junction protein and neurotrophic factor.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金资助项目(81573644);“十三五”期间天津市高等学校“创新团队培养计划”(TD13-5050);天津市2019年“131创新团队”项目