大鼠实验性高三酰甘油血症氧化损伤标志物研究

目的 建立大鼠高三酰甘油血症模型并观察模型鼠氧化损伤标志物及NADPH氧化酶的变化.方法60只雄性SD大鼠随机分为正常对照组、高三酰甘油血症模型组及阳性药物组,每组20只,模型组和阳性药物组采用高脂饲料喂养4周.测定基线及建模4周末的血清三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)及肝脏的TG、TC.以RT-PCR法检测建模6周末鼠肝NOX1-mRNA与NOX4-mRNA表达.阳性药物组4周末后以非诺贝特灌胃,剂量为100 mg·kg-1·d-1,持续2周后检测血清TG、HDL-C、LDL-C及TC.结果造模4周末,模型与阳性药物组血清TG、LDL-C、TC、肝脏TG、TC水平均较基线时明显升高(P<0.05);模型组与阳性药物组血清HDL-C明显低于其基线时水平(P<0.05).同时,模型组与阳性药物组血清MDA水平较基线时明显升高(P<0.05);SOD和GSH-PX较基线时明显降低(P<0.05).6周末模型组肝NOX1-mRNA与NOX4-mRNA表达均高于对照组与阳性药物组(P<0.05).阳性药物组经非诺贝特灌胃治疗2周后,血清TG、TC、LDL-C均明显下降(P<0.05),HDL-C明显上升(P<0.05).结论成功建立大鼠高三酰甘油血症模型,高三酰甘油血症大鼠GSH-PX和SOD明显降低,MDA明显上升,并通过激活体内NADPH氧化酶而诱导机体出现氧化损伤.

Study on oxidative damage markers in experimental rats with hypertriglyceridemia

Objective To establish rat model with hypertriglyceridemia in order to observe the changes of oxidative damage markers and NADPH oxidase in experimental rats with hypertriglyceridemia. Methods Sixty male SD rats were randomly divided into control group ( n=20 ) , model group ( n=20 ) and positive drug group ( n=20 ) . The rats in model group and positive drug group were feed with high fat diet for 4 weeks. The serum levels of TG,HDL-C,LDL-C,TC,MDA, SOD,GSH-PX and TG,TC in liver at baseline and on 4 weeks after modeling were detected. The expression levels of of NOX1-mRNA and NOX4-mRNA in liver were measured by RT-PCR at the end of 6 weeks after modeling. The rats in positive drug group were given fenofibrate by gavage,100 mg·kg-1 ·d-1 for 2 weeks, and then the levels of TG,HDL-C,LDL-C and TC were detected. Results At the end of 6 weeks after modeling,the levels of TG,LDL-C,TC and TG,TC in model group and positive drug group were significantly increased,as compared with those at baseline (P<0. 05),however,the serum levels of HDL-C were obviously decreased,as compared with those at baseline (P<0. 05). Meanwhile,the serum levels of MDA in model group and positive drug group were significantly higher than those at baseline (P<0. 05),but the levels of SOD and GSH-PX were significantly lower than those at baseline(P < 0. 05). The expression levels of liver NOX1-mRNA and NOX4-mRNA at the end of 6 weeks after modeling in model group were significantly higher than those in control group and positive drug group (P<0. 05). On 2 weeks after treatment with fenofibrate,the serum levels of TG,TC and LDL-C in positive drug group were obviously decreased, however,the serum levels of HDL-C were significantly increased (P < 0. 05). Conclusion The rat models with hypertriglyceridemia are successfully established. The levels of GSH-PX and SOD in rats with hypertriglyceridemia are obviously decreased and the levels of MDA were significantly increased,and then NADPH oxidase is activated to induce oxidative damage in vivo.