TRPV1在大鼠气管内注入胃液导致肺纤维化过程中的作用

Role of TRPV1 in pulmonary fibrosis induced by intratracheal administration of gastric juice in rats

目的探究瞬时感受器电位香草酸受体1(TRPV1)在大鼠气管内注入胃液导致肺纤维化过程中的作用。方法将30只SD大鼠随机分成对照组、模型组和辣椒平(CPZ)干预组,每组10只。模型组气管内注入大鼠胃液0.5ml/kg,每周1次,连续8周,对照组注入等量生理盐水,CPZ干预组注入胃液前30min腹腔注射CPZ10mg/kg。第9周取材,检测各组大鼠肺组织中羟脯氨酸含量,通过酶联免疫吸附试验方法检测各组大鼠支气管肺泡灌洗液(BALF)中转化生长因子β1(TGF-β1)水平,通过HE染色和Masson染色观察大鼠肺泡炎和肺纤维化程度,免疫组织化学和蛋白质印迹法检测大鼠肺组织中TRPV1、α-平滑肌肌动蛋白及Ⅰ型胶原蛋白的表达水平。结果模型组大鼠肺组织中TRPV1、α-平滑肌肌动蛋白及Ⅰ型胶原蛋白的表达水平,羟脯氨酸含量和肺纤维化评分均明显高于对照组(P值均<0.01),CPZ干预组大鼠肺泡炎及肺纤维化水平比模型组显著降低(P值均<0.05);与对照组比较,模型组大鼠BALF中TGF-β1水平显著增加(P<0.01),CPZ干预组大鼠BALF中TGF-β1水平低于模型组(P<0.05)。结论TRPV1的激活促进误吸胃液大鼠肺纤维化的发生。

Objective To investigate the effect of transient receptor potential vanilloid 1 (TRPV1) in the process of pulmonary fibrosis induced by intratracheal administration of gastric juice in rats. Methods Thirty SD rats were randomly divided into control group, model group and capsazepine (CPZ) intervention group, with ten rats in each group.Rats in model group were intratracheally injected with gastric juice (0.5 ml/kg) once a week for eight weeks.Rats in control group were injected with the same volume of normal saline.Rats in CPZ intervention group were intraperitoneally injected with CPZ (10 mg/kg) at 30 minutes before gastric juice was injected.At the ninth week, rats were sacrificed.Hydroxyproline content in the lung tissue of each group was detected.The level of transforming growth factor-β1 (TGF-β1) in bronchoalveolar lavage fluid (BALF) of each group was measured by enzyme-linked immunosorbent assay.The degrees of alveolitis and pulmonary fibrosis in rats were observed by HE staining and Masson staining.The expressions of TRPV1,α-smooth muscle actin and collagenⅠwere detected by immunohistochemistry and Western blot. Results The expressions of TRPV1,α-smooth muscle actin and collagenⅠ, and the content of hydroxyproline and the degree of pulmonary fibrosis in lung tissue of rats in the model group were significantly higher than those in the control group (all P<0.01). The degrees of alveolitis and pulmonary fibrosis in the CPZ intervention group were significantly lower than those in the model group (all P<0.05). Compared with the control group, the level of TGF-β1 in BALF of the model group was significantly increased (P<0.01), and the level of TGF-β1 in BALF of the CPZ intervention group was lower than that of the model group (P<0.05). Conclusions The activation of TRPV1 promotes the development of pulmonary fibrosis in rats with gastric juice aspiration.