【摘要】 目的:研究白藜芦醇(Resveratrol,Res)对妊娠期糖尿病大鼠脑组织氧化应激和细胞凋亡的影响。方法:取妊娠5天大鼠,通过腹腔注射链脲佐菌素(STZ)35 mg/kg的方法诱导制备妊娠期糖尿病大鼠模型,选取100只模型大鼠,根据血糖水平随机分为:妊娠期糖尿病模型对照组,白藜芦醇(60、120和240 mg/kg)治疗组和盐酸二甲双胍(200mg/kg)阳性对照组,每组20只;另取20只妊娠5天大鼠作为正常妊娠对照组,20只同龄非妊娠雌性大鼠作为正常非妊娠对照组。分别于给药前和给药后第7、14天分别测定各组大鼠空腹血糖水平;给药治疗2周后,测定各组大鼠血清中总抗氧化能力(T-AOC)水平和磷酸肌酸激酶(CPK)、乳酸脱氢酶(LDH)含量;检测脑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)活性和丙二醛(MDA)含量;通过HE染色观察脑组织病变,通过TUNEL染色观察神经细胞凋亡状况并计算凋亡指数。结果:与正常非妊娠对照组大鼠相比,正常妊娠组大鼠各监测指标无显著性变化。与正常妊娠对照组相比,妊娠期糖尿病模型对照组大鼠血糖水平显著升高,血清中T-AOC水平显著降低、CPK和LDH含量显著升高,脑组织中SOD、GSH-Px、CAT活性显著降低,且MDA含量显著升高;脑组织病理性形态学改变明显,神经细胞凋亡现象突出、凋亡率显著升高,上述差异均具有统计学意义。与妊娠期糖尿病模型组相比,白藜芦醇(120和240mg/kg)治疗组大鼠血糖水平显著降低,血清中CPK、LDH含量显著降低,脑组织中SOD、CAT活性显著降低且MDA含量显著降低;白藜芦醇(240mg/kg)治疗组血清中T-AOC水平和脑组织中GSH-Px活性均显著升高;白藜芦醇治疗组大鼠脑组织病变和神经细胞凋亡状况均明显改善,其中以240mg/kg治疗组效果最为显著,白藜芦醇(120和240mg/kg)治疗组神经细胞凋亡指数显著降低;上述差异均具有统计学意义。结论:白藜芦醇能够有效降低血糖,改善脑组织中抗氧化酶活性、降低氧化应激损伤,改善脑组织病变并抑制神经细胞凋亡,提示白藜芦醇对妊娠期糖尿病大鼠脑组织氧化应激和细胞凋亡具有抑制作用。更多还原

【Abstract】 Objective: To investigate the effect of resveratrol on brain tissue oxidative stress and apoptosis in gestational diabetic rat. Methods: 100 rats with gestation for 5 days were injected STZ( 35 mg / kg) by intraperitonal to make gestational diabetic model,which were randomly devided into five groups: gestational diabetic model control group,resveratrol( 60,120,240 mg / kg) treated groups and metformin hydrochloride200 mg / kg treated group; and selected 20 rats with gestation for five days as normal gestation control group and another 20 rats with no gestation as normal control group. Before and after the drugs were given for 7,14 days,the level of plasma glucose was determined. Two weeks later,the level of T-AOC and the content of CPK,LDH in serum were determined; the activity of SOD,CAT and the content of MDA in brain were determined; the histopathological changes of brain tissue and neurocyte apoptosis were observed,and the apoptotic index were calculated. Results: Compared with normal control group,all of the monitoring indicators in the normal gestation control group was not significantly different( P > 0. 05). Compared with normal gestation control group,the level of plasma glucose in gestational diabetic model group was significantly increased( P < 0. 01); the level of T-AOC in serum was significantly decreased and the content of ALT,AST,ALP were significantly increased( P < 0. 01); the activity of SOD,GSH-Px,CAT in brain were significantly decreased and the content of MDA was significantly increased( P < 0. 01); the brain tissue histopathological changes and neurocyte apoptosis were significant,the apoptotic index were significantly increased( P < 0. 01). Compared with the gestational diabetic model group,the level of plasma glucose in resveratrol( 120,240 mg / kg) treated groups were significantly decreased( P < 0. 05,P < 0. 01),the content of CPK,LDH in serum were significantly decreased( P< 0. 05,P < 0. 01),the activity of SOD,CAT in hepatic tissue were significantly increased and the content of MDA was significantly decreased( P < 0. 05,P < 0. 01); and the level of T-AOC in serum and the activity of GSH-Px in brain tissue of resveratrol 240 mg / kg treated group was significantly increased( P < 0. 01); the histopathological changes and the neurocyte apoptosis were significantly improved,the apoptotic index of resveratrol( 120,240 mg / kg) treated groups were significantly decreased( P < 0. 05,P < 0. 01). Conclusion: Resveratrol could effectively lower the level of plasma glucose,improve antioxidase activity,depress the oxidative stress,inhibit the histopathological changes of brain tissue and neurocyte apoptosis,which suggesting that resveratrol had protective effects on tissue oxidative stress and cell apoptosis in gestational diabetic rats.更多还原