番茄红素对实验性糖尿病大鼠肾脏保护作用的研究

Protective effects of Lycopene on the kidneys in experimental diabetic rats

目的研究番茄红素(Lycopene,LP)对实验性糖尿病大鼠肾脏的保护作用。方法首先通过高脂高糖饮食饲养8周后腹腔注射链脲佐菌素(STZ)方法制备糖尿病大鼠模型,将造模成功的80只大鼠随机分为模型组、番茄红素5 mg/kg组、番茄红素10 mg/kg组、番茄红素20 mg/kg组和盐酸二甲双胍组,每组16只。另取16只健康大鼠作为正常对照组。正常对照组和模型组连续灌胃生理盐水,番茄红素各组和盐酸二甲双胍组分别连续灌胃相应剂量番茄红素和盐酸二甲双胍(200 mg/kg),每天1次,连续28 d。分别于给药前和给药后第7,14,28天测定各组大鼠胰岛素和空腹血糖水平。给药28 d后,观察各组大鼠一般状况,测定各组大鼠体质量、肾脏指数、24 h尿量、24 h尿蛋白量(UPro)及血尿素氮(BUN)、肌酐(SCr)、尿酸(UA)水平;测定各组大鼠肾脏组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量;通过PAS染色观察肾脏组织病理形态学变化;通过TUNEL染色观察肾小球细胞凋亡状况,并计算凋亡指数(AI)。结果番茄红素各组大鼠一般状况得到明显改善,其中以20 mg/kg组效果最为显著。番茄红素10mg/kg组灌胃第28天胰岛素水平明显高于模型组,番茄红素20 mg/kg组灌胃第14,21,28天胰岛素水平均明显高于模型组。番茄红素20 mg/kg组灌胃第21,28天空腹血糖水平均显著低于模型组。番茄红素10 mg/kg组和番茄红素20 mg/kg组大鼠体质量显著高于模型组,肾脏指数、尿量、UPro及血清BUN、SCr、UA水平均显著低于模型组;肾脏组织中SOD活性显著高于模型组,MDA含量显著低于模型组,其中番茄红素20 mg/kg组GSH-Px活性显著高于模型组。番茄红素各组大鼠肾脏组织病理形态学改变和肾脏组织细胞凋亡状况均明显改善,其中以20 mg/kg组效果最为显著;并且番茄红素10 mg/kg组和番茄红素20 mg/kg组大鼠肾小球细胞凋亡指数显著低于模型组。结论番茄红素对实验性糖尿病大鼠肾脏组织具有保护作用。

Objective It is to investigate the protective effects of Lycopene （ LP） on the kidneys in experimental diabetic rats.Methods 80 diabetic rat models made by intraperitoneal injecting STZ after feeding with high fat and sugar diet for 8 weeks were randomly devided into 5 groups：model group, LP 5, 10, 20 mg/kg groups and Metformin hydrochloride group , each group had 16 rats.Another 16 same-aged rats were selected as normal control group .Normal control group and model group were given normal saline by intragastric administration , every LP group and Metformin hydrochloride group were treated with respective dosage of LP or Metformin hydrochloride （200mg/kg） once a day and for 28 days.Before and once week after the drug was given , the levels of insulin and blood sugar were determined .Four weeks later , the general status of the rats were observed;the body weight, renal index（RI）, 24h urine volume, UPro and the content of BUN, SCr, UA in serum were deter-mined;the activity of SOD , GSH-Px and the content of MDA in renal tissue were determined;the renal tissue histo-patho-logical changes was observed by HE staining;the apoptosis of renal cells was observed by TUNEL staining , and the apoptosis index（AI） was alculated.Results Compared with diabetic model group , the general status of the rats in LP treated groups were improved, especially in 20mg/kg group the improvements were more significant; the level of insulin in LP 10 mg/kg group was significantly higher than that in model group on the 28th day, while the levels in 20 mg/kg group on the 14th, 21th, 28th day were all higher than that in model group .The blood sugar level of LP 20 mg/kg group was significantly lower than that in model group on the 21th and 28th days;the body weight and SOD activity in LP 10, 20 mg/kg groups were significantly higher, while RI, urine volume, UPro and the levels of serum BUN, SCr, UA, MDA were lower than that in model group . The activity of GSH-Px of LP 20 mg/kg group was significantly higher than that in model group .The histopathological chan-ges and the apoptosis of the renal tissue in LP treated groups were significantly improved , especially in LP 20 mg/kg group the improvements were more significant , and AI of LP 10, 20 mg/kg groups were significantly lower than than in model group . Conclusion LP had dose-dependent protective effects on kidneys in experiment diabetic rats .