丹酚酸A对ZDF大鼠肾脏的保护作用和抑制脂蛋白相关磷脂酶A2的研究  

Protective effect of salvianolic acid A on kidney of ZDF rats and inhibition of lipoprotein-associated phospholipase A2

作　　者：陈姣姣 陈小真[1] 郁晨 徐松涛 施佳君 马全鑫[1] 陈民利[1] CHEN Jiaojiao;CHEN Xiaozhen;YU Chen;XU Songtao;SHI Jiajun;MA Quanxin;CHEN Minli(Animal Experimental Research Center/Institute of Comparative Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学动物实验研究中心/比较医学研究中心,杭州310053

出　　处：《中国比较医学杂志》2019年第2期25-31,共7页Chinese Journal of Comparative Medicine

基　　金：浙江省中医药管理局重点项目(2015ZZ009)

摘　　要：目的观察丹酚酸A(salvianolic acid A,SAA)对Zucker糖尿病肥胖(zucker diabetic fatty rat,ZDF)大鼠肾病的保护作用和对脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2,Lp-PLA2)表达的影响。方法取11～12周的雄性ZDF大鼠40只,根据体重与血糖,随机分为模型对照组、SAA 0. 25 mg/kg、0. 5mg/kg、1 mg/kg剂量组和阳性(25 mg/kg darapladib)对照组,每组8只,另取8只同周龄ZL大鼠作为正常对照组,各给药组每日给药一次,模型对照组和正常对照组每日给予同体积生理盐水,连续12周后,测定ZDF大鼠肾微循环血流速度,并检测血清中Lp-PLA2活性、尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Crea),尿中转铁蛋白(urinary transferrin,TRF)、微量白蛋白(microalbumin,mALB)和视黄醇结合蛋白(retinol binding protein,RBP)的含量以及肾组织中Lp-PLA2 mRNA与蛋白表达,同时进行肾脏组织病理学观察。结果与正常对照组比,模型对照组大鼠出现明显的肾脏病理结构改变和肾微循环血流速度明显降低(P<0. 01),而血清Lp-PLA2活性、BUN水平以及尿中TRF、mALB和RBP均明显升高(P<0. 01),并且肾组织中Lp-PLA2 mRNA和蛋白表达升高(P<0. 01);给予SAA和Lp-PLA2抑制剂(darapladib)后能明显改善上述指标的改变,且SAA给药组中以0. 5mg/kg、1 mg/kg剂量组改善尤为显著。结论 SAA对ZDF大鼠肾脏有明显的保护作用,其机制可能与抑制LpPLA2有关。Objective To observe the protective effect of salvianolic acid A(SAA)on nephropathy and the expression of lipoprotein-associated phospholipase A2(Lp-PLA2)in Zucker diabetes fatty rats(ZDF).Methods According to the body weight and blood glucose,40 male ZDF rats aged 11-12 weeks were randomly divided into five groups(n=8 per group),namely,a model group,0.25,0.5,and 1 mg/kg SAA groups,and a positive(Lp-PLA2 inhibitor at25 mg/kg)group.Meanwhile,another eight ZL rats of the same age were used as a normal group.Each drug administration group was given the corresponding drug once a day.Simultaneously,the model group and the normal group were administered normal saline of the same volume daily.After 12 weeks of continuous intervention,the renal microcirculation blood flow of ZDF rats was measured.Lp-PLA2 activity,blood urea nitrogen(BUN),and creatinine(Crea)in serum as well as transferrin(TRF),microalbumin(mALB),and retinol binding protein(RBP)in urine were analyzed.Lp-PLA2 mRNA and protein expression in renal tissue was also examined.Moreover,renal histopathological observation was performed.Results Compared with the control group,the pathological structure of the kidney was clearly changed and renal microcirculation blood flow was significantly decreased in the model group(P<0.01),whereas serum Lp-PLA2 activity and BUN levels and urinary TRF,mALB,and RBP were all notably increased(P<0.01).Moreover,the expression of Lp-PLA2 mRNA and protein in renal tissues was markedly increased(P<0.01).The changes of these indicators were dramatically ameliorated after the administration of SAA and Lp-PLA2 inhibitor,especially in the groups with SAA at doses of 0.5 and 1 mg/kg.Conclusions SAA can improve the symptoms of DN in type2 diabetic rats,which may be related to the inhibition of Lp-PLA2 activity and mass.

关 键 词：丹酚酸A ZDF大鼠 2型糖尿病肾病 脂蛋白相关磷脂酶A2(Lp-PLA2) 

分 类 号：R-33[医药卫生]