Huangqi Decoction,a compound Chinese herbal medicine,inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-βaxis

Objective Huangqi Decoction(HQD),a classical traditional Chinese medicine formula,has been used as a valid treatment for alleviating liver fibrosis;however,the underlying molecular mechanism is still unknown.Although our previous studies showed that microRNA-663a(miR-663a)suppresses the proliferation and activation of hepatic stellate cells(HSCs)and the transforming growth factor-β/small mothers against decapentaplegic(TGF-β/Smad)pathway,whether long noncoding RNAs(lncRNAs)are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported.The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.Methods The expression levels of lnc-C18orf26-1,miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction.HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs.The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs.Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs.RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs.Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA.The expression levels of collagen α-2(I)chain(COL1A2),α-smooth muscle actin(α-SMA)and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.Results Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a.Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation,downregulated TGF-β1-stimulatedα-SMA and COL1A2 expression,and inhibited the TGF-β1/Smad signaling pathway.HQD suppressed the proliferation and activation of HSCs.HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs.Further studies showed that HQD inhibited the expression of COL1A2,α-SMA,TGF-β1,TGF-βtype I receptor(TGF-βRI)and phosphorylated Smad2(p-Smad2)in HSCs,and these effects were reversed by miR-663a inhibitor treatment.Conclusion Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis.HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.

补肾活血汤联合西药治疗气阴两虚型糖尿病肾病Ⅳ期水肿随机平行对照研究

[目的]观察补肾活血汤联合西药治疗气阴两虚型糖尿病肾病IV期水肿疗效。[方法]使用随机平行对照方法,将72例住院患者按随机数字表方法随机分为两组,均常规治疗,控制饮食(低盐、优质低蛋白糖尿病饮食);控制血糖(胰岛素控制血糖:空腹血糖≤7.0retool/L,餐后2h血糖≤10.0retool/L,糖化血红蛋白<7.0%);控制血压(<130/80mmHg)。对照组36例洛汀新10mg,2次/d。治疗组36例补肾活血汤(黄芪30g,生地黄15g,山药20g,山茱萸15g,茯苓30g,泽泻、丹皮、当归、川芎各15g,赤芍20g,白术10g,泽兰15g,大腹皮20g,车前草15g)水煎,1剂/d。观测中医症状积分、生化指标。30d为1疗程,连续治疗1疗程,随访60d,判定疗效。[结果]中医症状积分两组均有降低(P<0.01),治疗组优于对照组(P<0.05);水肿均有消退,治疗组优于对照组(P<0.01);APTT、PT、FIB治疗组有改善(P<0.05),对照组均无明显改善(P>0.05),治疗组优于对照组(P<0.05);CHOL、TG、UP治疗组均明显减少(P<0.01,P<0.05),对照组无显著变化(P>0.05),组间差异显著(P<0.05,P<0.01)。[结论]补肾活血汤可改善糖尿病肾病的高凝状态、调节血液流变学、改善脂代谢异常,对糖尿病肾病性水肿具有较好的治疗作用,实现对肾脏的保护作用。