吡非尼酮及盐酸氨溴索对百草枯诱导的大鼠急性肺损伤保护作用的比较

Protective Effects of Pirfenidone and Ambroxol Hydrochloride Against Paraquat-Induced Lung Damage in Rats

目的比较吡非尼酮(pirfenidone,PF)及盐酸氨溴索(ambroxol hydrochloride,AH)对百草枯(paraquat,PQ)诱导的大鼠急性肺损伤的保护作用。方法 40只雄性成年SD大鼠随机分为正常对照组、PQ组、PQ+PF组、PQ+AH组,采用腹腔注射20%PQ溶液诱导大鼠急性PQ中毒模型。苏木精-伊红(HE)染色评价肺组织损伤情况;测定肺组织湿重/干重比(W/D);测定各组大鼠肺组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)、谷胱甘肽(GSH)含量变化;ELISA法检测血清中肿瘤坏死因子α(TNF-α)及白细胞介素(IL-6)含量。结果与正常对照组大鼠相比,PQ组大鼠肺组织肺泡萎缩,部分过度膨胀,组织炎性侵润和纤维化明显,肺组织氧化应激水平明显升高,肺组织W/D增加,血浆中TNF-α及IL-6含量增加;与PQ组相比,给予PF或AH治疗后大鼠肺组织损伤和纤维化降低,大鼠肺组织氧化应激水平降低,肺组织W/D降低,血浆中TNF-α及IL-6含量降低。PF与AH组相比,各指标差异无统计学意义。结论 PF和AH均可以减轻PQ中毒大鼠肺组织损伤,其治疗作用可能与其抗炎抗氧化有关。

Objective To study the protective effects of pirfenidone （PF） and ambroxol hydrochloride （AH） against paraquat （PQ）-induced lung damage in rats and its underlying mechanisms. Methods Fourty rats were randomly divided into four groups： control group, PQ group, PQ--PF group, and PQ＋AH group. The poisoning model was induced by intragastrically administering 20 percent PQ solution （25 mg/kg）. The rat lung tissue morphological changes were observed with HE staining, the ratio of wet to dry lung tissue （W/D） was examined, the activity of superoxide dismutase （SOD）, the eontent of malondialdehyde （MDA） and giutathione （GSH） were examined in the lung tissue, the content of IL 6 and TNF-a were determined using enzyme-linked immunosorbent assay （ELISA） kits. Results Compared with the control rats, the degree of lung damage was severe, the levels of oxidative stress and the ratio of W/D were increased, and the IL 6 and TNF-a in the serum were increased. Compared with the PQ rats, PF or AH exhibited significant decrease in oxidative stress and inflammation, the ratio of W/D and the IL- 6 and TNF-a in the serum were also decreased. There was no difference between PF and AH groups. Conclusion The results indicate that PF and AH has a protective effect against PQ-induced lung damage in rats. It is considered that this protective effect may be related to its free radical scavenging activity, and inhibition of inflammation.