Objective: To investigate the impact of transforming growth factor-β1 (TGF-β1) silencing by small interfering RNA (siRNA) on the expression of platelet-derived growth factor-β (PDGF-BB) and its receptor (PDGF-βR) in rats with hepatic fibrosis. Methods: A total of 40 male Sprague-Dawley rats were randomly divided into normal control group, model group, TGF-β1 siRNA treatment group, and negative control group. All rats except those in the normal control group were given subcutaneous injection of 40% carbon tetrachloride to establish a rat model of hepatic fibrosis. The rats in the negative control group and the TGF-β1 siRNA treatment group were given tail vein injection of negative control plasmid or TGF-β1 siRNA plasmid twice a week at a dose of 0.25 mg/kg, and those in the normal control group and the model group were given the injection of sterile isotonic saline twice a week. The rats were sacrificed after 12 weeks and liver tissue samples were collected. Real-time PCR, immunohistochemistry, and Western blot were used to measure the expression of PDGF-BB, PDGF-βR, and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) in liver tissue. A one-way analysis of variance, the q test, and the Kruskal-Wallis test were used for statistical analysis based on data type. Results: Compared with the model group and the negative control group, the TGF-β1 siRNA treatment group had significantly inhibited mRNA and protein expression of PDGF-BB and PDGF-βR (F = 24.785 and 22.92, P < 0.01), as well as significantly inhibited expression of p-ERK1/2 (P < 0.05). Conclusion: Targeted TGF-β1 siRNA can effectively downregulate the expression of PDGF-BB, PDGF-βR, and p-ERK1/2 in liver tissue and thus help to improve hepatic fibrosis.
目的： 研究靶向小干扰RNA沉默转化生长因子β1（TGFβ1）对肝纤维化大鼠体内血小板衍生生长因子β（PDGF-BB）及其受体（PDGF-βR）表达的影响。 方法： 将40只雄性SD大鼠随机分为4组:正常对照组、模型组、TGFβ1 siRNA治疗组、阴性对照组。除正常对照组外，其余各组均给予40%四氯化碳皮下注射诱导大鼠肝纤维化模型。阴性对照组和TGFβ1 siRNA治疗组经大鼠尾静脉分别按0.25 mg/kg注射阴性对照质粒、TGFβ1 siRNA质粒，正常组与模型组注射无菌等渗盐水，每周2次。12周后处死大鼠，取肝组织样本，分别采用Real-Time PCR、免疫组织化学及Western blot检测PDGF-BB、PDGF-βR及磷酸化细胞外调节蛋白激酶（p-ERK1/2）在大鼠肝组织的表达。据资料不同分别采用单因素方差分析、q检验或Kruskal-Wallis检验进行统计学分析。 结果： 与模型组、阴性对照组相比，TGFβ1 siRNA能显著抑制肝组织中PDGF-BB及PDGF-βR的mRNA和蛋白的表达（F值分别为24.785、22.920，P<0.01）；TGFβ1 siRNA还能明显抑制肝组织中p-ERK1/2的表达（P<0.05）。 结论： 靶向TGFβ1 siRNA可以有效地下调肝组织中PDGF-BB、PDGF-βR及p-ERK1/2的表达从而起到改善肝纤维化的作用。.