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目的:本实验以妊娠期糖尿病大鼠为研究对象,探讨白藜芦醇对妊娠期糖尿病大鼠肾脏组织抗氧化和抗炎的作用。方法:实验用雌性大鼠经高脂高糖饲料喂养8周后与雄鼠合笼过夜制备孕鼠,5 d后采用ip链脲佐菌素(STZ,35 mg·kg~(-1))破坏胰岛β细胞的方法诱导制备糖尿病大鼠,选取80只模型大鼠根据血糖水平随机分为模型组、白藜芦醇60,120,240 mg·kg~(-1)组治疗组和盐酸二甲双胍(200 mg·kg~(-1))阳性药组,并另取16只同批妊娠5 d大鼠作为正常妊娠组,以及16只同龄非妊娠雌性大鼠作为正常非妊娠组;判定造模成功后立即ig给药,每天1次,疗程2周。给药治疗前和治疗完成后分别观察各组大鼠一般状况;治疗完成后测定各组大鼠空腹血糖水平,测量24 h尿量并测定24 h尿蛋白量(UPro),检测血清中血尿素氮(BUN),肌酐(SCr),尿酸(UA)含量,通过PAS染色观察肾脏组织病变,通过原位末端转移酶标记法(TUNEL)染色观察肾脏组织细胞凋亡状况并计算凋亡指数;测定血清中总抗氧化能力(T-AOC)水平和肾脏组织中超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px),过氧化氢酶(CAT)活性以及丙二醛(MDA)含量,检测血浆中炎症因子C-反应蛋白(CRP),肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β),白细胞介素-6(IL-6),细胞间黏附分子-1(ICAM-1)水平。结果:正常妊娠组大鼠各监测指标与正常非妊娠组比较均无显著性差异;与正常妊娠组比较,模型组大鼠“三多一少”症状明显,血糖水平显著升高,24 h尿量显著增多,UPro显著增高,血清中BUN,SCr,UA含量显著升高,呈现明显的肾脏组织病变和肾细胞凋亡、凋亡指数显著升高,血清中T-AOC水平和肾脏组织中SOD,GSH-Px,CAT活性均显著降低,MDA含量显著升高,上述差异均具有统计学意义(P<0.05,P<0.01);与模型组比较,白藜芦醇治疗组大鼠一般状况明显改善,“三多一少”症状明显减轻;白藜芦醇120,240 mg·kg-1治疗组大鼠空腹血糖水平显著降低,24 h尿量显著减少,UPro显著降低,血清中BUN,SCr,UA含量显著降低,肾脏组织病变和肾细胞凋亡状况均明显改善、凋亡指数显著降低,肾脏组织中SOD,CAT活性显著升高且MDA含量显著降低,并且240 mg·kg-1治疗组大鼠血清中T-AOC水平和肾脏组织中GSH-Px活性均显著升高,上述差异均具有统计学意义(P<0.05,P<0.01)。结论:白藜芦醇对妊娠期糖尿病大鼠肾脏组织抗氧化和抗炎能力具有改善作用。
OBJECTIVE: In this study, gestational diabetes mellitus rats were used to investigate the effects of resveratrol on the anti-oxidative and anti-inflammatory effects of kidney in gestational diabetic rats. METHODS: Female rats were fed with high-fat and high-sucrose diet for 8 weeks and caged overnight with male rats to prepare pregnant rats. Five days later, ip streptozotocin (STZ, 35 mg · kg -1) Methods 80 diabetic rats were randomly divided into model group, 60, 120 and 240 mg · kg -1 resveratrol groups and metformin hydrochloride (200 mg · kg -1) kg ~ (-1)) positive group. Another 16 pregnant rats of the same batch were used as normal pregnancy group and 16 non-pregnant female rats of the same age as normal non-pregnancy group. Administration, 1 day, 2 weeks treatment. Before treatment and after treatment, the general condition of rats in each group was observed. After fasting, fasting blood glucose level was measured in each group, urine volume was measured for 24 hours and UPro was measured for 24 hours, blood urea (BUN), creatinine (SCr) and uric acid (UA) were measured. The pathological changes of renal tissues were observed by PAS staining and the apoptotic index of renal tissues were observed by TUNEL staining. Serum total antioxidant capacity (T-AOC) and renal tissue superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activity and malondialdehyde (MDA), and the levels of inflammatory cytokines C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin- , Intercellular adhesion molecule-1 (ICAM-1) levels. Results: Compared with normal pregnancy group, the monitoring indicators of normal pregnancy group had no significant difference compared with normal non-pregnancy group. The symptoms of “three, less and one less” in model group were significantly higher and blood glucose level was significantly increased h urine volume increased significantly, UPro significantly increased serum BUN, SCr, UA content was significantly increased, showing significant renal tissue lesions and renal cell apoptosis, apoptosis index was significantly increased serum T-AOC levels and kidney tissue (P <0.05, P <0.01). Compared with the model group, the resveratrol treatment group rats were generally lower than those in the model group The symptoms of “three more and less” significantly reduced; resveratrol 120,240 mg · kg-1 treatment group rats significantly lower fasting blood glucose levels, urine output decreased significantly 24 h, UPro significantly lower serum levels of BUN , SCr, UA were significantly decreased, renal tissue lesions and renal cell apoptosis were significantly improved, apoptosis index was significantly reduced, SOD and CAT activity was significantly increased and MDA content was significantly decreased, and 240 mg · kg-1 The level of T-AOC in serum and the activity of GSH-Px in kidney tissue in treatment group were significantly increased, It said differences were statistically significant (P <0.05, P <0.01). Conclusion: Resveratrol can improve the anti-oxidation and anti-inflammatory abilities of kidney in gestational diabetic rats.