黄连温胆汤对糖尿病合并脑梗死大鼠血糖、神经功能缺失及血管内皮生长因子表达的影响

Effect of Huanglian Wendan Decoction on expression of blood glucose,neurological deficit and vascular endothelial growth factor of rats with diabetes mellitus and cerebral infarction

目的观察黄连温胆汤对糖尿病合并脑梗死大鼠血糖、神经功能缺失及血管内皮生长因子(VEGF)表达的影响及其可能的机制。方法选取清洁级成年SD大鼠72只,随机分为假手术组、模型组、阳性对照组、黄连温胆汤大剂量组、黄连温胆汤中剂量组、黄连温胆汤小剂量组。糖尿病动物模型造模成功后,所有大鼠普通饲料喂养4周。除假手术组外,其余各组进行缺血性脑卒中模型复制(线栓法建立大鼠大脑中动脉闭塞模型),而假手术组只做分离不结扎。术后每天用青霉素腹腔注射以预防感染,连续3 d。造模成功后,黄连温胆汤大、中、小剂量组每天分别给予黄连温胆汤0.24、0.12、0.06 g/kg体重溶于2 m L生理盐水灌胃,1次/d;假手术组及模型组给予生理盐水灌胃2 m L/次,1次/d;阳性对照组每天给予血塞通6 mg/kg体重溶于2 m L生理盐水灌胃,1次/d。于糖尿病造模后72 h、造卒中模后与治疗14 d后各检测1次血糖,观察大鼠神经功能缺损情况,按酶联免疫吸附测定法检测大鼠脑组织内VEGF蛋白水平。结果与模型组比较,黄连温胆汤大、中、小剂量组以及阳性对照组均能显著降低大鼠血糖水平(P<0.05或P<0.01),减轻神经功能缺损症状(P<0.05),降低大鼠脑组织VEGF含量(P<0.05);同时黄连温胆汤大、中、小剂量组在这些方面与阳性对照组之间差异无统计学意义(P>0.05)。结论黄连温胆汤可调节VEGF,神经功能缺损的改善可能与VEGF含量的改变相关。

Objective To observe the effect of Huanglian Wendan Decoction on expression of blood glucose, neurological deficit and vascular endothelial growth factor （VEGF） of rats with diabetes mellitus and cerebral infarction and its possible mechanism. Methods 72 clean adult SD rats were chosen and randomly divided into sham operation group, model group, positive control group, Huanglian Wendan Decoction high dose group, Huanglian Wendan Decoction medium dose group, Huanglian Wendan Decoction low dose group. After the success building of animal models of diabetes mellitus, all rats were fed with normal diet for four weeks. In addition to the sham operation group, the other groups made replication of ischemic stroke model （suture-occluded method was used to establish middle cerebral artery occlusion model in rats）, the sham operation group only took separation without ligation. Intraperitoneal injection of Penicillin every day after operation was used to prevent infection, for 3 days continuously. After the success building of model, Huanglian Wendan Decoction high, medium, low dose group was given Huanglian Wendan Decoction 0.24, 0.12, 0.06 g/kg weight into 2 mL saline for gavage, once a day; the sham operation group and model group were given saline for gavage, once 2 mL; the positive control group was given Xuesaitong 6 mg/kg weight into 2 mL saline for gayage, once a day, The blood glucose was detected for one time respectively after the establishment of diabetes mellitus for 72 h, after the establishment of stroke model, and after treatment for 14 d. The conditions of neurologic impairment in rats were observed. The protein level of VEGF in brain tissue of rats was detected by enzyme-linked immunosorbent assay. Results Compared with model group, Huanglian Wendan Decoction high, medium, low dose group and positive control group could significantly decrease the levels of blood sugar of rats （P 〈 0.05 or P 〈 0.01）, reduce the symptoms of neurologic impairment （P 〈 0.05）, lower the contents of VEGF in brain tissue of rats （P 〈 0.05）; while Huanglian Wendan Decoction high, medium, low dose group had no significant differences compared with positive control group in the indexes above （P 〉 0.05）. Conclusion Huanglian Wendan Decoction can adjust VEGF, and the improvement of neurologic impairment may be correlated with the changes of VEGF contents.