石荠苧总黄酮对博来霉素致大鼠肺纤维化的治疗作用及其机制

Effects of Total Flavonoids from Mosla Scabra on Bleomycin-induced Pulmonary Fibrosis of Rats and It's Mechanism

关键词:  石荠苧总黄酮  肺纤维化  博来霉素  NF-κB  TGF-β1

Key words:  total flavonoids from Mosla scabra  pulmonary fibrosis  bleomycin  NF-κB  TGF-β1

摘要:

目的 观察石荠苧总黄酮（MSF）对博来霉素致大鼠肺纤维化的干预作用，并初步探讨其机制。方法 60只SD大鼠随机分为正常组，模型组，阳性对照组，MSF低、中、高剂量组，气道注射博来霉素（5 mg·kg^-1）制备大鼠肺纤维化模型。造模14 d后，阳性对照组给予2 mg·kg^-1醋酸泼尼松，MSF低、中、高剂量组分别给予40，80，160 mg·kg^-1，正常组和模型组给予等量生理盐水，每天1次，连续28 d，于造模42 d后检测血清超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、白细胞介素-4（IL-4）、肿瘤坏死因子-α（TNF-α）、转化生长因子-β1（TGF-β1）和透明质酸（HA）含量，Masson染色观察纤维化发展情况，免疫组化检测α-肌动蛋白（α-SMA）表达，蛋白印迹检测核因子-κB（NF-κB）、TGF-β1、TNF-α、Smad2/3和pSmad2/3表达情况。结果 与模型组相比，MSF干预后大鼠血清SOD、GSH活性显著增加；IL-4、TNF-α、TGF-β1和HA含量显著降低（P<0.01）；α-SMA表达明显下调，纤维化程度减轻；NF-κB、TNF-α、TGF-β1、Smad2/3和pSmad2/3表达显著降低（P<0.01）。结论 MSF对肺纤维化具有一定的治疗作用，其机制可能与抑制NF-κB和TGF-β1通路信号转导有关。

Abstract:

OBJECTIVE To investigate protective effects of total flavonoids from Mosla scabra(MSF) on bleomycin- induced pulmonary fibrosis of rats, and explore its preliminary mechanism. METHODS Sixty SD rats were divided into six groups randomly: normal group, model group, positive control group, MSF high-dose, middle-dose and low-dose treatment group. Pulmonary fibrosis in rats was induced by intratracheal instillation of belomycin (5 mg·kg^-1). After challenge of 14 d, the two treatment groups were given MSF at the doses of 40, 80 and 160 mg·kg^-1 respectively, while positive control group was treated with prednisone acetate (2 mg·kg^-1). Normal group and model group were treated with saline once a day for 28 d. The activities of SOD and GSH, the levels of IL-4, TNF-α, TGF-β1 and HA in serum were detected after molding 42 d. The histological examination was performed with Masson stain. The expression of α-SMA was detected by immunohistochemistry analysis while the expression of NF-κB, TNF-α, TGF-β1, Smad2/3 and pSmad2/3 proteins was detected by Western-blotting analysis.RESULTS Compared with the model group, the activities of SOD and GSH were increased significantly whereas levels of IL-4, TNF-α, TGF-β1 and HA in serum were decreased significantly after MSF treatment (P<0.01). The expression of a-SMA was down-regulated. The degree of fibrosis was reduced. The protein expressions of NF-κB, TNF-α, TGF-β1, Smad2/3 and pSmad2/3 were also significantly decreased (P<0.01). CONCLUSION MSF can ameliorate pulmonary fibrosis through inhibition of NF-κB and TGF-β1 signaling.