乌司他丁对大鼠百草枯中毒急性肺损伤的治疗作用

Experimental study on therapeutic effect of Ulinastatin on acute lung injury of rats associated with Paraquat poisoning

目的评估乌司他丁对大鼠百草枯(PQ)中毒急性肺损伤的影响。方法 35只雄性SD大鼠,按随机数字表法分成正常对照组(A组)5只、PQ中毒模型组(B组)15只、乌司他丁组(C组)15只。B组与C组禁食1 h后经口一次灌胃PQ 75 mg/kg制成百草枯中毒急性肺损伤模型,A组经口一次性注入等量生理盐水;C组腹腔注射乌司他丁10万单位/d,共3 d,A组与B组给予0.2 ml/d生理盐水腹腔注射。A组于造模后24 h,B、C两组大鼠于造模后24、48、72 h分别取5只大鼠肺组织与血清。肺组织行HE染色,血清测定肿瘤坏死因子-α(TNF-α)、转化生长因子β1(TGF-β1)。结果 B组血清TNF-α在第24小时即出现显著统计学差异,且持续存在;血清TGF-β1造模后24 h即升高,在第48小时与A组比较有差异,在72 h则出现显著统计学差异(P<0.01)。C组与B组比较,血清TNF-α升高缓慢,在第24小时即有统计学差异(P<0.05),持续至第72小时;而两组大鼠的TGF-β1比较却无统计学差异(P>0.05)。结论乌司他丁可以减轻百草枯中毒急性肺损伤,但对TGF-β1的影响有限,可能通过其他途径减缓中毒后的肺纤维化过程。

Objective To investigate the preventive effects of Ulinastatin （UTI） on acute lung injury（ALI） of rats associated with Paraquat （PQ） poisoning. Methods A total of 35 SD rats were divided into control group （ Group A, n = 5 ）, PQ group （ Group B ,n = 15 ） and UTI group （Group C ,n = 15 ）according to random number table. Group B and Group C were induced by PQ feeding （75 mg/kg） after one hour＇s fasting so as that ALI models would be made. Group A was fed with an equal amount of normal sa- line. Group C received UTI （ 100,000 U/d, once daily） via intraperitoneal injection for three days, and Group A and Group B re- ceived normal saline （0.2 mE/d）. Lung tissue specimens and sera were taken from Group A （ at 24 hours） and from Group B and Group C （ at 24 - , 48 - and 72 hours）, respectively. The hmg tissue specimens were treated with HE staining. The contents of tumor necrosis factor-α （TNF-oL） and transforming growth faetor-β1 （TGF-13j ） in the sera were measured. Results The TNF-α of Group B significantly increased at 24 hours and at the later hours, and the TGF-β1 began to increased at 24 hours, significantly in- creased at 48 hours and more significantly increased at 72 hours when compared with that of Grout3 A （P 〈 0.0i）. Compared with that of Group B, the TNF-α of Group C increased slowly at 24 hours （ lasting to 72 hours） （P 〈 0.05） , and the TGF-β1 was of no significant difference （ P 〉 0.05 ）. Conclusion UTI can reduce ALI caused by PQ poisoning. It may slow pulmonary fibrosis after poisoning by other means, in consideration of its limited influence on TGF-β1.