[目的]探究二苯乙烯苷(TSG)调控Klotho蛋白对慢性肾脏病(CKD)小鼠肾纤维化的影响。[方法]30只C57BL/6J小鼠随机分为对照组(Control)、模型组(CKD)、模型+二苯乙烯苷处理组(CKD+T)，取肾组织检测各组小鼠肾功能[24 h尿蛋白(UP)、24h尿白蛋白(UA)，血肌酐(SCr)，尿素氮(BUN)]、氧化应激指标[肾超氧化物歧化酶(SOD)，丙二醛(MDA)，尿8-羟基脱氧鸟苷(8-ohdg)]，RT-PCR检测Klotho mRNA表达，Western Blot检测肾组织纤维化相关因子[中性粒细胞明胶酶相关脂质运载蛋白(NGAL)，纤连蛋白(FN)，结缔组织生长因子(CTGF)]及Klotho 蛋白表达。[结果]与 Control 组相比，CKD 组、CKD+T 组的 24 h UP、24 h UA、ACR、SCr、BUN、尿 8-ohdg、肾MDA、NGAL、FN、CTGF蛋白表达水平均升高，肾SOD、Klotho mRNA及蛋白表达水平降低，且CKD+T组的24 h UP、24 h UA、ACR、SCr、BUN、肾MDA、尿8-ohdg含量、肾小管损伤评分、胶原纤维阳性面积(14。1±2。7 vs 6。4±1。5)％、NGAL、FN、CTGF 蛋白表达水平低于 CKD 组，肾 SOD、Klotho mRNA 及蛋白表达量(1。21±0。23 vs 1。46±0。29，1。18±0。16 vs 1。37±0。21)高于CKD组(P＜0。05)。[结论]TSG可改善CKD小鼠肾功能，抑制氧化应激反应和延缓肾纤维化进程，可能是通过上调Klotho蛋白表达来起作用的。
Inhibition of tetrahydroxystilbene glucoside on renal fibrosis in mice with chronic kidney disease via regulating soluble Klotho protein expression
[Objective]To explore the effect of tetrahydroxystilbene glucoside(TSG)on renal fibrosis in mice with chronic kid-ney disease(CKD)via regulating soluble Klotho protein expression.[Method]Thirty C57BL/6J mice were randomized to one of three interventions:1)control(Control group),2)CKD model construction(CKD group)and 3)CKD model construction+TSG treatment(CKD+T group).Renal tissues were collected to measure renal function parameters[24 hours urinary protein(UP),24 hours urinary albumin(UA),serum creatinine(SCr),blood urea nitrogen(BUN),urinary albumin/creatinine ratio(ACR)]and oxidative stress indexes[superoxide dismutase(SOD),malondialdehyde(MDA),8-hydroxydeoxyguanosine(8-ohdg)]of mice in each group.Klotho mRNA expression was detected by real time polymerase chain reaction(RT-PCR),and the protein expression levels of fibrosis-related factors[neutrophil gelatinase-associated lipocalin(NGAL),fi-bronectin(FN),connective tissue growth factor(CTGF)]and Klotho protein expression were tested by Western Blot.[Re-sult]Compared with control group,CKD group and CKD+T group were found to have an elevation in the values of 24 hours UP,24 hours UA,ACR,SCr,BUN,urinary 8-ohdg and renal MDA as well as the protein expression of NGAL,FN,and CTGF,and also reported a decrease in renal SOD plus the mRNA and protein expression of Klotho.In addition,the values of 24 hours UP,24 hours UA,ACR,SCr,BUN,renal MDA and urinary 8-ohdg content,the renal tubular injury score,the collagen fiber positive area(14.1±2.7 va 6.4±1.5)％,along with the protein expression of NGAL,FN,and CTGF were lower in CKD+T group than in CKD group,and the renal SOD,Klotho mRNA expression(1.21±0.23 vs 1.46±0.29)and Klotho protein ex-pression(1.18±0.16 vs 1.37±0.21)were higher in CKD+T group than in CKD group,with statistical difference(all P＜0.05).[Conclusion]TSG can inhibit the expression of fiber-related factors and delay the process of renal fibrosis in CKD mice,which may be related to the down-regulation of soluble Klotho protein expression.
万方数据
维普
