贯叶连翘提取物对百草枯所致肺纤维化的干预作用

The effective of extract of hypericum perforatum L in the rat model of acute paraquat intoxication

[论文特点介绍]研究证明贯叶连翘具有清除自由基和抗氧化的作用。圆盘状受体1（discoidin domainreceptor 1）是一类带有盘状结构域的受体型酪氨酸激酶，研究表明在肺中DDR1有显著的表达。在特发性间质肺纤维化患者支气管肺泡液中的细胞中。DDR1被激活后能使各种趋化因子增多引起细胞外基质沉积。由此可见DDR1的表达程度与肺纤维化程度密切相关。本研究为百草枯中毒所致肺纤维化提供新的思路，

Background and objective Acute paraquat （PQ） intoxication can cause severe lung injury, which typically shows alveolar dropsy, pulmonary hemorrhage, and can develop to pulmonary interstitial fibrosis, leading to respiratory failure and death. There has no specific antidote for the routine treatment of paraquat intoxication. Lung is the target organ of PQ. There are a lot of oxyradical. Hypericum perforatum L Ex maybe have an important role in the development of lung injury and pulmonary fibrosis. poisoned behind creates a lot of oxyradieal and lead to lipid peroxidation. It is the point of pulmonary fibrosis. In recent years, look for the plant of clearance oxyradical to used for an anti- fibrosis have already caused a domestic and international attention .Some researchs prove Exeract of Hypericum perforatum L （HP） can clear up oxyra dical to used for an anti- fibrosis, the expression of the DDR1 and TGF-β1 levels are important factors in pulmonary fibrosis. We measure the expression of the TGF-β1 and DD R1 in paraquat intoxication and interfered by HP in order to observe ability of anti- fibrosis of HP. Methods Forty mate Wister rats were randomized to four groups： Normal controlled group （group 1- N）： the control rats were given equivalent volume of normal saline ;acute paraquat intoxication model group （group 2-P）： the rats were given paraquat at the dose of 80 mg/kg by stomach perfusion. HP treated groups （group 3,4,5-H）： the rats were given paraquat at the dose of 80 one hour give HP100 mg/kg,200 mg/kg,400 mg/kg mined at 7th, 14th days post exposure. Fibrosis lev mg/kg twice a day for seven days by stomach perfusion, after Measurements were deterel of pulmonary fibrosis in acute paraquat intoxication was detected by HE, Masson tinction .The intensity of expression of TGF-β1, DDR1 was detected by immunohistochemistry. Results （1）Progressive diffuse airsacculitis, with alveolar dropsy, pulmonary hemorrhage, hyaline membrane and inflammatory cell infiltration was found in PQ intoxicated rats. HP treated groups（both group 3,4,5） can slow down the development of the progressive diffuse airsacculitis compared with acute paraquat intoxication group. HP treated groups（both group 3,4,5） can reduce collagen＇s hyperplasia compare with cute paraquat intoxication group. The levels of pulmonary fibrosis were significantly lower in HP treated groups（both group 3,4,5） compared with the rats of acute paraquat intoxication model 80 mg/kg（P〈 0.05）. The intensity of the TGF-β1 expression measured by immunohistochemistry, was significantly lower in HP treated groups（both group 3,4,5） compare with the rats of acute paraquat intoxication model （group 2）, （r=-0.855,P=0.000）. The intensity of the DDR1 expression measured by immunohistochemistry, was significantly lower in HP treated groups（both group 3,4,5） compare with the rats of acute paraquat intoxication model （group 2）, （r=-0.826,P=0.000）. Every group compare with each other has significantly different （P 〈0.05）. Conclusions These results suggest that the expression of TGF-β1 and DDR1 plays an important role in the pathogenesis of lung injury induced by acute paraquat intoxication. HP could alleviate the lung injury and fibrosis from reducing the expression of TGF-β1 and DDR1. HP may have a role in diminishing the level of pulmonary fibrosis induced by acute paraquat intoxication by clearing up oxyradical. HP is a effective medicine to treat pulmonary fibrosis induced by acute paraquat intoxication.