Anti-miR34c树状纳米颗粒对裸鼠肝纤维化的治疗作用

Delivery of anti-miR34c by polyamidoamine dendrimer attenuates hepatic fibrosis in nude mice

目的探索anti-miR34c树状纳米颗粒对裸鼠肝纤维化的治疗效果。方法将清洁级(20±2)g裸鼠随机分为正常组、模型组、anti-miR34c树状纳米颗粒治疗组,每组5只,腹腔注射四氯化碳诱导肝纤维化模型。HE染色观察肝组织病理变化,Masson染色评价胶原沉积情况,ELISA检测血清生化指标,免疫组化检测TGF-β和α-SAM在肝组织中的表达变化。结果 anti-miR34c树状纳米颗粒治疗组的肝组织炎症细胞浸润减少,胶原沉积降低,肝纤维化指标TGFβ和α-SAM表达降低,血清生化指标好转。结论 anti-miR34c的树状纳米颗粒能够有效改善裸鼠肝纤维化肝损伤,有望成为治疗肝纤维化的新策略。

Objective Upregulation of miR34 in the liver has been found in numerous liver diseases,from fatty liver disease to hepatocellular carcinoma.In the present study,we examined the protective actions of anti-miR34c polyamidoamine(PAMAM)dendrimer nanoparticles on hepatic fibrosis in nude mice.Methods Fifteen clean nude mice were randomly divided into the normal control,model control,and anti-miR34c PAMAM dendrimer nanoparticles groups(n=5 per group).Hepatic fibrosis was induced by intraperitoneal injection of 100μL of 20%carbon tetrachloride twice weekly for 6weeks.Hepatic pathology,serum biochemical indicators,and transforming growth factor-β(TGF-β)/α-smooth muscle cell actin(α-SMA)immunohistochemistry were examined.Results Anti-miR34c delivered by the PAMAM dendrimer decreased inflammatory cell infiltration,collagen deposition,and TGF-βandα-SAM expression in the liver,and improved serum biochemical factors.Conclusions Anti-miR34c PAMAM dendrimer nanoparticles can improve hepatic fibrosis by reducing activation of HSC and incidence of liver injury in nude mice.