Objective To explore the possible mechanisms of 5-HT2A receptor involved in the proliferation of pulmonary artery smooth muscle cells. Methods Pulmonary hypertension rat models were established by intraperitoneal injection of monocrotaline. Rats in the treatment group were treated with 5-HT2A receptor antagonists (sarpogrelate hydrochloride) for three weeks while those in the control group were intraperitoneally given sodium chloride. The morphological changes of peripheral pulmonary artery were observed with hematoxylin and eosin staining method; the expressions of TGF-β1 and PKC in the pulmonary artery were detected by Western blotting and RT-PCR. Results Compared with the control group, mPAP and RV/(LV + S)% were increased significantly in the model group (both P<0. 05). The endothelial cells shedded or disappeared, the pulmonary artery wall thickened, and the lumen narrowed. In the model group, the protein and mRNA expressions of TGF-β1 and PKC were increased. Compared with the model group, mPAP and RV/(LV + S)% decreased markedly in the treatment group (P<0.05; P<0.01). The media thickness and stenosis in the treatment group were significantly improved. In the treatment group, the protein and mRNA expressions of TGFβ1 and PKC were decreased (P<0. 05; P<0.01). Conclusion 5-HT2A receptor antagonists can reduce pulmonary artery pressure and improve the pulmonary arterial remodeling induced by pulmonary arterial hypertension through PKC/TGF-β1 signal pathway.%目的 探讨5-HT2A受体参与肺动脉平滑肌细胞增殖的可能机制.方法 腹腔注射野百合碱建立肺动脉高压大鼠模型;5-HT2A受体拮抗剂(盐酸沙格雷酯)灌胃3周为干预组;腹腔注射生理盐水为对照组.HE染色观察肺动脉结构的变化;RT-PCR和Western blotting技术检测蛋白激酶C(PKC)和转化生长因子β1(TGF-β1) mRNA及蛋白的表达.结果 与对照组相比,模型组大鼠平均肺动脉压力(mPAP)、右室肥厚指数明显升高(P均＜0.05);内皮细胞脱落消失,肺动脉管壁增厚,管腔狭窄;肺动脉中TGF-β1、PKC蛋白及mRNA的表达明显升高.与模型组相比,干预组mPAP、右室肥厚指数明显降低(P＜0.05,P＜0.01);中膜厚度及管腔狭窄程度也明显改善;肺动脉中TGF-β1、PKC蛋白及mRNA表达明显降低(P＜0.05,P＜0.01).结论 5-HT2A受体拮抗剂可降低肺动脉压力,改善肺动脉高压导致的肺动脉重塑,其作用可能是通过PKC/TGFβ1途径实现的.
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