蒙药扫日劳-4味汤对特发性肺纤维化模型大鼠的改善作用及机制初探
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篇名: 蒙药扫日劳-4味汤对特发性肺纤维化模型大鼠的改善作用及机制初探
TITLE: Preliminary Study on Improvement Effects of Mongolian Medicine Saorilao- 4 Decoction on Specific Pulmonary Fibrosis Model Rats and Its Mechanisms
摘要: 目的:初步探讨蒙药扫日劳-4味汤对特发性肺纤维化模型大鼠的改善作用及机制。方法:将雄性SD大鼠随机分为正常对照组、模型组、阳性对照组(吡非尼酮,0.163g/kg)和扫日劳-4味汤低、中、高剂量组(0.899、1.798、3.596g/kg),每组8只。除正常对照组外,其余各组大鼠均按5mg/kg于气管内缓慢注射6mg/mL博来霉素1次以复制特发性肺纤维化模型。从建模后的第1天起,正常对照组和模型组大鼠灌胃生理盐水,其余各组大鼠灌胃相应药液,每天1次,给药体积均为10mL/kg,连续给药4周。实验期间,观察各组大鼠的一般情况并称定其体质量。末次给药24h后,观察各组大鼠肺的外观形态,采用苏木精-伊红和Masson染色观察肺组织形态学特征,采用酶联免疫吸附法测定其血清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,肺组织中羟脯氨酸(HYP)、白细胞介素1β(IL-1β)、IL-6、透明质酸酶(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(Col-Ⅳ)含量,采用实时荧光定量聚合酶链式反应技术测定其肺组织中转化生成因子β(1TGF-β1)、Smad3、Smad7mRNA的表达水平。结果:与模型组比较,扫日劳-4味汤各剂量组和阳性对照组大鼠活动、毛发、饮食等均有明显改善,末次给药后的体质量均显著升高,肺组织病理改变和肺纤维化特征均明显改善,血清中SOD活性显著升高,血清中MDA含量(扫日劳-4味汤中剂量组除外)和肺组织中HYP(扫日劳-4味汤高剂量组除外)、IL-1β、IL-6、HA、LN、PC-Ⅲ、Col-Ⅳ(扫日劳-4味汤高剂量组除外)含量以及TGF-β1、Smad3mRNA的表达水平均显著降低,Smad7mRNA的表达水平均显著升高(P<0.05或P<0.01)。结论:扫日劳-4味汤可以显著改善特发性肺纤维化模型大鼠肺部病理改变,延缓并逆转肺纤维化进展,其机制可能与抑制炎症反应,改善脂质过氧化,下调TGF-β1、Smad3mRNA表达,上调Smad7mRNA表达有关。
ABSTRACT: OBJECTIVE:To preliminarily investigate the improveme nt effects and mechanism of Mongolian medicine Saorilao-4 decoction on specific pulmonary fibrosis model rats. METHODS :Male SD rats were randomly divided into normal control group ,model group ,positive control group (pirfenidone,0.163 g/kg)and Saorilao- 4 decoction low ,medium and high dose groups (0.899,1.798,3.596 g/kg),8 rats in each group. Except for normal control group ,other groups were given 6 mg/mL bleomycin intratracheally at 5 mg/kg once to induce the specific pulmonary fibrosis model. From the first day after modeling , normal control group and model group were given normal saline intragastrically ,other groups were given corresponding drugs intragastrically,once a day ,10 mL/kg,for 4 weeks. During the experimental period ,the general condition of the rats in each group was observed and the body mass was weighed. Twenty-four h after last medication ,the appearance morphology of rat l ung in each group were observed. The morphological characteristics of lung tissues were observed by HE and Masson staining. ELISA was adopted to determine the activity of SOD and the content of MDA in serum ,the contents of hydroxyproline (HYP),IL-1β,IL-6,hyaluronidase(HA),laminin(LN)precollagen type Ⅲ(PC-Ⅲ)and collagen type Ⅳ(Col-Ⅳ)in lung tissue. RT-PCR was used to determine the mRNA 发。E-mail:bwf007007@sina.com expression of TGF-β 1,Smad3 and Smad 7 in lung tissue. RESULTS:Compared with model group ,the activity ,hair and diet of the rats in each dose group of Saorilao- 4 decoction and positive control group were significant ly improved ,and the body mass after the last administration was significantly increased ; the pathological change of lung and pulmonary fibrosis were significantly improved ,and the activity of SOD in serum was increased significantly. Serum content of MDA (except for Saorilao- 4 decoction medium dose group ),the contents of HYP (except for Saorilao- 4 decoction high dose group ),IL-1β,IL-6,HA,LN,PC-Ⅲ,Col-Ⅳ(except for Saorilao- 4 decoction high dose group)as well as mRNA expression of TGF-β1 and Smad 3 in lung tissue were significantly decreased ;mRNA expression of Smad 7 was significantly increased (P<0.05 or P<0.01). CONCLUSIONS :Saorilao-4 decoction can significantly improve the lung pathological changes ,delay and reverse the progression of pulmonary fibrosis in specific pulmonary fibrosis model rats ,the mechanism of which may be related to the inhibition of inflammatory response , improvement of lipid peroxidation , down-regulation of TGF-β1 and Smad 3 mRNA expression ,and up-regulation of Smad 7 mRNA expression.
期刊: 2021年第32卷第12期
作者: 白万富,刘玉键,李想,王朋,常虹,郝海梅,白迎春,刘全礼,石松利
AUTHORS: BAI Wanfu, LIU Yujian,LI Xiang,WANG Peng,CHANG Hong,HAO Haimei,BAI Yingchun,LIU Quanli,SHI Songli
关键字: 特发性肺纤维化;蒙药;扫日劳-4味汤;炎症因子;氧化应激;转化生长因子β1/Smad信号通路;大鼠
KEYWORDS: Specific pulmonary fibrosis ;Mongolian medicine ;Saorilao-4 decoction;Inflammatory factors ;Oxidative stress ;
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