目的 研究注射用血栓通（凍干）（XST）減輕糖尿病大鼠海馬神經(jīng)損傷的作用。方法 ip鏈脲佐菌素（STZ）制備糖尿病大鼠模型，隨機分為模型組和XST（50 mg/kg）組，每組10只，另隨機取10只SD大鼠為對照組。ip給藥，每天給藥1次，于屏障環(huán)境中連續(xù)給藥60 d，對照組和模型組大鼠ip等量生理鹽水。常規(guī)HE染色觀察大鼠海馬CA1區(qū)細胞的形態(tài)；采用實時熒光定量PCR（qRT-PCR）技術對海馬Bax、Bcl-2、Bcl-xl、腦源性神經(jīng)營養(yǎng)因子（BDNF）、膠質細胞源性神經(jīng)營養(yǎng)因子（GDNF）、神經(jīng)突觸素（Syn）mRNA水平進行檢測；采用Western blotting法對3種緊密連接蛋白——海馬閉鎖小帶蛋白1（ZO-1）、咬合蛋白（Occludin）、封閉蛋白5（Claudin-5）和BDNF蛋白表達水平進行檢測。結果 與模型組比較，XST減輕糖尿病引起的海馬神經(jīng)細胞形態(tài)改變，顯著增加細胞數(shù)目（P<0.05） ；顯著升高抑凋亡基因Bcl-2、Bcl-xlmRNA的表達，降低促凋亡基因Bax mRNA的表達（P<0.05） ；XST組3種緊密連接蛋白的表達量均不同程度的升高，其中Occludin、Claudin-5差異有統(tǒng)計學意義（P<0.05、0.01）；XST組GDNF、BDNF mRNA表達、BDNF蛋白表達均顯著升高（P<0.05）。結論 XST可以減輕糖尿病大鼠海馬神經(jīng)損傷，其機制可能與提高緊密連接蛋白及神經(jīng)營養(yǎng)因子表達有關。

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.

R285.5

國家自然科學基金資助項目（81573644）；“十三五”期間天津市高等學?！皠?chuàng)新團隊培養(yǎng)計劃”（TD13-5050）；天津市2019年“131創(chuàng)新團隊”項目