人参对自发性糖尿病小鼠的肾脏保护作用及机制研究

Study on Nephroprotective Effect and Mechanism of Ginseng in Spontaneously Diabetic Mice

目的观察人参对自发性2型糖尿病(db/db)小鼠糖脂代谢、炎症反应及氧化应激的影响,探讨其肾脏保护作用的内在机制。方法选取8周龄雄性自发性2型糖尿病db/db小鼠18只,分为模型组、人参组、二甲双胍组,另取同周龄雄性同窝野生型db/m小鼠6只为正常组,干预9周后测量小鼠的体质量、6小时尿蛋白定量(six hours urinary total protein,6hUTP)及尿微量白蛋白与尿肌酐比值(albumin/urine creatinine ratio,ACR)。采用病理染色观察小鼠肾脏病理改变。检测血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low-density lipoprotein cholesterol,LDL-C)、糖化血清白蛋白(glycated serum protein,GSP)、血肌酐(serum creatinine,SCr)、血尿素氮(blood urea nitrogen,BUN)水平,以及氧化应激指标过氧化氢酶(catalase,CAT)、丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)水平,炎症因子白细胞介素1β(interleukin1β,IL-1β)、白介素6(interleukin 6,IL-6)、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)水平。结果与正常组比较,模型组小鼠体质量、ACR、6hUTP显著升高(P<0.01),肾脏病理可见肾小球肥大,系膜细胞增殖,系膜基质扩张,纤维组织增生,大片炎细胞浸润等典型表现,血清TG、TC、GSP、BUN、MDA、IL-1β、IL-6、TNF-α显著升高(P<0.05),SOD、CAT显著下降(P<0.05)。与模型组比较,人参组上述指标均有改善(P<0.05或P<0.01),且能显著降低SCr(P<0.01)。与二甲双胍组比较,人参组上述指标差异无统计学意义。结论人参可能通过改善炎症反应、氧化应激,调节糖血脂代谢,发挥对糖尿病小鼠肾脏的保护作用。

Objective To observe the effects of Ginseng on glucolipid metabolism,inflammatory response,and oxidative stress in spontaneous type 2 diabetic db/db mice and to explore the underlying mechanisms of renal protective effects of Ginseng.Methods 18 8-week-old male spontaneous type 2 diabetic db/db mice were selected and divided into the model group,Ginseng group,and Metformin group.6 male wild-type db/m mice of the same litter at the same week of age were selected as a control group.All indexes were measured after 9 weeks of intervention.Six hours urinary total protein(6hUTP)and albumin/creatinine ratio(ACR)were measured and the pathological changes of the kidney in mice were observed by pathological staining.The serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),glycated serum protein(GSP),creatinine(Cr),blood urea nitrogen(BUN)levels,as well as oxidative stress indexes catalase(CAT),malondialdehyde(MDA),superoxide dismutase(SOD)levels,inflammatory factors Interleukin 1β(IL-1β),Interleukin 6(IL-6),Tumor Necrosis Factor α(TNF-α)levels were all measured.Results Compared with the normal control group,model group mice had higher body mass,ACR and 6hUTP(P<0.01).Their renal pathology showed typical manifestations of diabetic nephropathy such as glomerular hypertrophy,the proliferation of thylakoid cells,expansion of thylakoid stroma,the proliferation of fibrous tissue,and extensive infiltration of inflammatory cells.Their serum TG、TC、GSP、BUN、MDA、IL-1β、IL-6、TNF-α were higher( P< 0.05),SOD,CAT were significantly decreased( P< 0.05).Compared with the model group,the above indexes in the ginseng group were improved(P<0.05,P<0.01),and SCr levels of Ginseng group were significantly reduced( P< 0.01).Compared with the metformin group,there was no significant difference in the above indexes in Ginseng group.Conclusion Ginseng can provide good protection to the kidney of spontaneously diabetic mice by improving inflammatory response,oxidative stress,and regulating lipid metabolism.