双氢青蒿素对百草枯致小鼠肺纤维化的治疗研究

目的:探讨双氢青蒿素(dihydroartemisin,DHA)对急性百草枯(paraquat,PQ)染毒小鼠的治疗作用。方法:将134只小鼠随机分成3组:正常对照组(n=24)、PQ染毒组(n=55,实际存活24只)和DHA治疗组(n=55,实际存活35只)。PQ组与DHA组:以100mg/kg PQ一次性灌胃;2h后DHA组以20mg/kg DHA灌胃治疗,PQ组与对照组灌胃等量蒸馏水,每日1次。观察给药后第3,7,14,21天小鼠的一般情况,比较生存率差异,计算肺系数,酶联免疫吸附法(ELISA)测定肺组织TGF-β1的表达;HE及Masson染色观察小鼠肺组织病理变化。结果:PQ组21d生存率与对照组和DHA组比较差异有统计学意义(P<0.05)。PQ组肺组织中TGF-β1在第3,7,14,21天分别为(467.77±46.52)ng/L、(434.89±48.94)ng/L、(1 410.70±94.07)ng/L、(2 306.89±33.06)ng/L;DHA组一般情况较PQ组好,TGF-β1表达在第3,7,14,21天时分别为(441.54±23.58)ng/L、(443.22±46.83)ng/L、(750.49±29.96)ng/L、(1 554.95±92.30)ng/L,较PQ组差异显著(P<0.01)。随时间推移,PQ组肺泡炎加重,14d始伴随着TGF-β1的升高,肺组织出现纤维化改变,以第21天时最为明显,与对照组比较差异明显(P<0.01)。DHA组炎性细胞浸润较PQ组少,充血水肿轻,肺纤维化程度较PQ组减轻(P<0.05)。结论:DHA可能通过降低肺组织中TGF-β1表达,发挥对PQ中毒小鼠肺纤维化的治疗作用。

THE CURATIVE EFFECT OF DIHYDROARTEMISININ ON PARAQUAT-INDUCED PULMONARY FIBROSIS IN A MICE MODEL

Objective:To study the curative effects of dihydroartemisin(DHA) on pulmonary fibrosis induced by paraquat(PQ) in mice.Methods: A total of 134 mice were randomly assigned into control(n=24),PQ(n=55,survivals 24) and DHA groups(n=55,survivals 35).PQ(100 mg/kg) was administered to the animals in PQ group and DHA group only once by intragastric administration.Two hours later,DHA group was cured by intragastric administration of 20 mg/kg DHA,control and PQ groups were given the equivalent distilled water once a day.The mice were killed on days 3,7,14 and 21.The indexes of test included general conditions,differences in survivals,and lung coefficient.TGF-β1 in the lung tissues,pulmonary inflammation and fibrosis of mice in different groups were observed by pathological methods(HE staining and Masson staining).Results: The survival rate on 21th day in PQ group was highest than that in DHA and control groups(P<0.05).TGF-β1 levels in lung tissues in PQ group on days 3,7,14 and 21 were(467.77±46.52),(434.89±48.94),(1410.70±94.07),and(2306.89±33.06) ng/L;respectively.DHA group got the lighter general conditions.The ELISA results of TGF-β1 were(441.54±23.58),(443.22±46.83),(750.49±29.96),and(1554.95±92.30) ng/L on days 3,7,14 and 21,as compared with PQ group(P<0.01).The pathological changes of PQ group became severer than the control group as time went by.On 14th day,PQ group showed pulmonary fibrosis in pathomorphology with an increasing of TGF-β1 and peaked on the 21th day,as compared with control group(P<0.01),and DHA group showed milder lung tissue inflammation and edema than PQ group(P<0.05).Conclusion: ① A pulmonary fibrosis model of mice can be successfully established by intragastric administration of 100 mg/kg PQ;② the increased TGF-β1 levels might be the result of pulmonary fibrosis;③DHA could reduce pulmonary fibrosis induced by PQ in mice lungs in a way of reducing TGF-β1.