中药注射液血必净联合激素防治鼠百草枯中毒后的肺损伤

Effects of Xuebijing injection combined with dexamethasone in prevention and treatment of rats＇ pulmonary injury induced by Paraquat

目的探讨中药注射液血必净联合激素对大鼠百草枯中毒急性慢性肺损伤的防治作用及可能机制。方法雄性Wistar大鼠120只平均随机分六组，每组20只：正常组（A），中毒组（B），治疗组（C，D，E，F）。除A组予等量生理盐水外，其余各组予20％百草枯（PQ）100mg／kg腹腔注射（ip）染毒2h后，C，D，E，F组分别予血必净（1．25g／kg）、血必净（2．5g/kg）、地塞米松（25mg／kg）、血必净（2．5g/kg）＋地塞米松（25mg／kg），ip，A，B组予等量生理盐水治疗，1次／d，至处死，而28d处死者治疗7d。观察各组大鼠反应，于染毒后2，3，4d每组每天各处死5只，检测血清超氧化物歧化酶（SOD）、丙二醛（MDA）及3d动脉血气、肺系数；于28d处死剩余鼠，测定肺匀浆羟脯氨酸（HYP）、血清TGV-β1。A，B，F组行3d，28d肺病理检查。结果治疗组中毒症状较B组轻，F组最轻；各治疗组不同时间点SOD，MDA及血气，TGF-β1，HYP较B组佳，治疗组中F组最佳，其中B，F组的3d时的SOD，MDA及28d时的HYP，TGV-β1分别为（37．47±13．00）nmol／mL，（91．86±21．35）nmol／mL；（11．34±3．07）nmol／mL，（5．63±1．58）nmol／mL；（2．54±0．63，1．32±0．07）mg／g；（484．13±63．79，202．22±49．83）pg／mL，差异均具有统计学意义（P〈0．05）。肺病理显示F组急性期肺出血、肺实变及慢性期肺纤维均较B组轻。结论血必净联合激素于中毒早期有较强清除氧自由基、抑制脂质过氧化反应的能力，可以减轻急性肺出血、肺水肿；晚期通过抑制TGV-β1分泌和HYP的合成，减轻慢性肺纤维化。

Objective To explore the prevention and treatment effect and its mechanism of Xuebijing injection combined with dexamethasone on rats＇ paraquat-induced acute and chronic pulmonary injury. Method One hundred and twenty of male Wistar rats were randomly divided into six groups：normal group（A）, administrated with saline ; model group（B） and treatment groups（ group C, D, E, F） were given 20% PQ （ 100 mg/kg, ip）, and 2 hours later the normal and model groups were administrated with the same volume of saline for treatment, rats in group C and group D received 1.25 g/kg and 2.5 g/kg Xuebijing injection respectively, rats in group E received 25 mg/kg dexamethasone, rats in group F receired 2.5 g/kg Xuebifing injection combined with 2.5 g/kg dexamethasone, one time per day till to be killed, while rats killed at 28 d were treated for 7 days. At 2 d, 3 d, 4 d after poisoned,five rats in each group were killed,serum SOD,MDA level and arterial gas （at 3 d） were measured. At 28 d,the rest of rats were killed, and serum TGF-β1, lung tissure HYP were measured. The pathology of the lung tissue was observed at 3 d and 28 d in guoup A, B, F. Results Compared with group B, poisoning symptoms in the treatment groups were milder and serum SOD, MDA, TGF-β1, lung fissure HYP level were better, arterial oxygen content were higer. Among treatment groups, the treatment effects in group F were the best, SOD and MDA of 3 d, HYP and TGF- β1 of 28 d in group B and F were respectively （37.47 ± 13.00,91.86 ± 21.35） nmol/mL; （11.34 ±3.07,5.63 ± 1.58） nmol/mL; （2.54 ± 0.63, 1.32 ± 0.07） mg/g; （484.13 ± 63.79,202.22 ± 49.83） pg/mL. The difference was significant（ P 〈 0.05）. The pathology of the lung tissue showed that acute lung hemorrhage, edema or chronic pulmonary fibrosis in group F were milder than that of group B. Conclusions In early stage, Xuebijing injection combined with dexamethasone has a stronger ability to clear out oxidized free radical and inhibit lipid super oxidized reaction. This may ameliorate acute pulmonary blooding and edema. In later stage, they could ameliorate chronic pulmonary fibrosis by inhibiting TGF-β1 secretion and HYP generation.