山楂叶总黄酮对2型糖尿病大鼠脑组织的保护作用

Protection of Hawthorn Leaves Favonoids for Brain in Type 2 Diabetic Rats

目的研究山楂叶总黄酮(hawthorn leaves favonoids,HLF)对2型糖尿病大鼠脑组织损伤的保护作用。方法通过高脂高糖饮食8周后腹腔注射链脲佐菌素(STZ)的方法诱导制备2型糖尿病大鼠模型,选取100只随机分为:糖尿病模型对照组、山楂叶总黄酮(50、100、200mg/kg)治疗组和盐酸二甲双胍(200mg/kg)阳性对照组,另取20只同龄大鼠作为正常对照组;每天灌胃给药1次,疗程6周。分别于给药前和给药后第2周、第4周和第6周测定各组大鼠空腹血糖水平;6周后,测定各组大鼠血浆中磷酸肌酸激酶、乳酸脱氢酶活性和丙二醛含量;测定各组大鼠脑组织中超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶活性和丙二醛含量;并通过苏木精-伊红(HE)染色观察脑组织病变;通过TUNEL染色观察各组大鼠神经细胞凋亡并计算凋亡指数。结果较糖尿病模型对照组,山楂叶总黄酮200mg/kg治疗组大鼠空腹血糖水平显著降低(P<0.01);山楂叶总黄酮100、200mg/kg治疗组大鼠血浆中磷酸肌酸激酶、乳酸脱氢酶活性和丙二醛含量均显著降低(P<0.05,P<0.01),脑组织中超氧化物歧化酶、过氧化氢酶活性显著升高且丙二醛含量显著降低(P<0.05,P<0.01);山楂叶总黄酮200mg/kg治疗组大鼠脑组织中谷胱甘肽过氧化物酶显著升高(P<0.05)。山楂叶总黄酮各治疗组大鼠脑组织病变和神经细胞凋亡均明显改善,其中200mg/kg治疗组效果最为显著,并且100、200mg/kg治疗组大鼠神经细胞凋亡指数显著降低(P<0.05,P<0.01)。结论山楂叶总黄酮能够有效降低2型糖尿病大鼠空腹血糖、改善脑组织病变、抑制神经细胞凋亡,提示山楂叶总黄酮对2型糖尿病大鼠脑组织损伤具有剂量依赖性的保护作用,其作用机制可能与其能够有效改善抗氧化酶活性、降低氧化应激损伤有关。

Objective To investigate the protection and mechanism of Hawthorn leaves favonoids（HLF） on brain injury of type 2 diabetic rats. Methods One hundred diabetic rat-models made by feeding with high fat and sugar and intraperitoneal injecting STZ were randomly devided into five groups：diabetic model control group, HLF（50, 100 and 200mg/kg） treated groups and metformin hydrochloride 200mg/kg treated group, and normal control group （20 same-aged rats）. The drugs were given by intragastric administration for 6 weeks, once a day. Before the duge was given and after 2, 46 weeks, the level of blood sugar was determined. And 6 weeks later, the activity of CPK, LDH and the content of MDA in serum were determined. The activity of SOD, GSH-Px, CAT and the content of MDA in brain tissue were also determined. The histopathological changes of the brain tissue was observed by HE staining. The nerve cells apoptosis were observed by TUNEL staining, and the apoptosis Index（AI） were analysised. Results Compared with the diabetic model group, the level of blood sugar in HLF 200mg/kg treated group was significantly decreased （P〈0.01）. The activity of CPK, LDH and the content of MDA in serum of HLF 100, 200mg/kg treated groups were significantly decreased （P〈0.05, P〈0.01）, and the activity of SOD, CAT in brain tissue were significantly increased （P〈0.05, P〈0.01）. The activity of GSH-Px in HLF 200mg/kg treated group was significantly increased（P〈0.05）. The brain tissue histopathological changes and nerve cells apoptosis were significantly improved, especially the HLF 200mg/kg treated group, and the AI of HLF 100, 200mg/kg treated group was significantly decreased（P〈0.05, P〈0.01）. Conclusion HLF could effectively lower the level of blood sugar, improve the brain tissue histopathological changes, depress the nerve cells apoptosis, suggesting that HLF had protective effects on brain tissue in type 2 diabetic rats; whose mechanism perhaps related to its effects on enhanceing the activity of antioxidant enzymes, inhibiting the damage of oxidative stress.