摘要
目的探究积雪草苷对链脲佐菌素(STZ)诱导的大鼠糖尿病及其并发肝肾损伤的保护作用。方法取40只SPF级SD大鼠随机分为对照组、模型组、积雪草苷8、16、32 mg/kg组。除对照组外,其余各组大鼠腹膜内注射链脲佐菌素(streptozotocin,STZ)(65 mg/kg)。3 d后测尾静脉空腹血糖高于16.7 mmol/L,表示建模成功。积草雪苷各剂量组大鼠腹膜内注射相应剂量药物,对照组和模型组大鼠腹膜内注射等量生理盐水,每天1次,持续4周。检测尾静脉空腹血糖、肥胖指数,全自动生化分析仪检测尿蛋白、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血清尿素氮(BUN)和血清肌酐(Scr),qRT-PCR和WB检测诱导型一氧化氮合酶(iNOS)、白细胞介素(IL)-6、IL-1β和IL-10表达;取肝脏和肾脏进行HE染色,观察肝肾组织病理形态学变化,Western印迹法检测肾脏组织中线粒体凋亡通路相关蛋白的表达和AKT/GSK3β的磷酸化。结果积草雪苷16 mg/kg和32 mg/kg明显降低DM大鼠血糖、肥胖指数和尿蛋白含量(P<0.05),以及血清中HDL、LDL、TG、TC、ALT、AST、BUN、Scr、iNOS、IL-6、IL-1β和IL-10水平(P<0.05);明显减轻DM大鼠肝肾组织病理损伤,减少炎性细胞浸润;显著减少DM大鼠肝肾组织细胞凋亡率,逆转DM大鼠cleaved Cas-9/Cas9、cleaved Cas-3/Cas3、p-AKT/AKT和p-GSK3β/GSK3β比值的上调(P<0.05)。结论积草雪苷对DM具有显著的降糖降脂功效,对DM并发的肝肾功能损伤也起到重要的保护作用,其作用机制可能与AKT/GSK3β通路有关。
Objective To investigate the protective effect of asiaticoside on streptozotocin(STZ)-induced diabetes and liver and kidney injury in rats.Methods Forty SPF SD rats were randomly divided into control group,model group,and asiaticoside 8 mg/kg,16 mg/kg,and 32 mg/kg groups.Except for the control group,rats in the other groups were injected intraperitoneally(ip)with streptozotocin(STZ)(65 mg/kg).After 3 days,the fasting blood glucose in the tail vein was higher than 16.7 mmol/L,indicating that the modeling was successful.The rats in the asiaticoside groups were intraperitoneally injected with corresponding doses of drugs,and the rats in the control group and the model group were intraperitoneally injected with the same amount of normal saline,once a day for 4 weeks.The tail vein fasting blood glucose and obesity index were tested.Urinary protein,total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL),high-density lipoprotein(HDL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum urea nitrogen(BUN)and serum creatinine(Scr)were detected by automatic biochemical analyzer.Expression levels of inducible nitric oxide synthase(iNOS),interleukin(IL)-6,IL-1βand IL-10 were detected by qRT-PCR and Western blotting.Then liver and kidney tissues were harvested for HE staining,and the pathomorphological changes of liver and kidney tissues were observed Western blotting was employed to detect the expression of mitochondrial apoptosis pathway related protein and AKT/GSK3βphosphorylation in kidney tissue.Results 16 mg/kg and 32 mg/kg of asiaticoside can significantly reduce blood glucose,obesity index and urine protein content in DM rats(P<0.05),as well as HDL,LDL,TG,TC,ALT,AST,BUN,Scr,iNOS in serum,IL-6,IL-1βand IL-10 levels(P<0.05).The pathological damage of liver and kidney tissue in DM rats was significantly reduced;inflammatory cell infiltration was also reduced;the apoptosis rate of liver and kidney tissue in DM rats was significantly reduced,and the ratios of cleaved Cas-9/Cas9 reversed,cleave
作者
祝瑜
赵宇
谭彦
蒋德熊
张诚
ZHU Yu;ZHAO Yu;TAN Yan;JIANG Dexiong;ZHANG Cheng(Department of Clinical Medicine,Dazhou Vocational and Technical College,Dazhou,635000,China;Department of Hepatobiliary Surgery,Dazhou Central Hospital,Dazhou,Sichuan Province,635000,China;Department of Ultrasound Medicine,The Third People’s Hospital of Dazhou(Dachuan District People’s Hospital),Dazhou,635000,Sichuan Province,China;Department of Respiratory Medicine,Dazhou Central Hospital,Dazhou,Sichuan Province,635000,China;Department of Laboratory The Third People’s Hospital of Dazhou(Dachuan District People’s Hospital),Dazhou,635000,Sichuan Province,China)
出处
《医学分子生物学杂志》
CAS
2021年第5期372-379,共8页
Journal of Medical Molecular Biology
基金
四川省科技厅应用基础研究项目(No.2018JY0324)。
关键词
糖尿病
积草雪苷
丙氨酸转氨酶
血清肌酐
蛋白激酶B/糖原合成酶激酶3β
diabetes
asiaticoside
alanine aminotransferase(ALT)
serum creatinine(Scr)
protein kinase B/glycogen synthase kinase(AKT/GSK3β)
