百草枯中毒大鼠肺组织ACE和ACE2基因表达及二巯丙磺钠的保护作用

目的 探讨急性百草枯(PQ)中毒大鼠肺组织中血管紧张素转化酶(ACE)、血管紧张素转化酶2(ACE2)的基因表达及二巯丙磺钠(Na-DMPS)的保护作用.方法 100只SD雄性大鼠分为正常对照组(10只)、Na-DMPS对照组(10只)、PQ染毒组和Na-DMPS保护组(各40只).PQ染毒组和Na-DMPS保护组大鼠一次性腹腔注射PQ 20 mg/ks,其中保护组大鼠于染毒前15 min以Na-DMPS 200mg/kg腹腔注射进行保护.观察各组大鼠在中毒后6、24 h及3、7d各时间点的临床表现和光学显微镜下肺脏的组织学改变,并使用反转录一聚合酶链反应(RT-PCR)方法测定各组大鼠各时间点肺组织ACE和ACE2 mRNA的表达.结果 PQ染毒组大鼠染毒后出现呼吸急促、抽搐,呈进行性加重,Na-DMPS保护组大鼠中毒症状出现延后且明显减轻.光学显微镜下可见,染毒组大鼠肺组织损伤的表现以肺部毛细血管和肺泡结构破坏、肺泡内渗出物增多、炎症细胞聚集为主,而Na-DMPS保护组大鼠肺组织受损则相对较轻.各时点PQ染毒组肺组织ACE及ACE2 mRNA的表达均下降,在24 h时ACE mRNA表达为0.457±0.262,3 d时为0.385±0.179;3 d时ACE2 mRNA表达为0.415±0.247,7 d时为0.365±0.215,与正常对照组(ACE mRNA为0.781±0.354,ACE2 mRNA为0.761±0.420)和Na-DMPS对照组(ACEmRNA为0.765±0.364,ACE2mRNA为0.725±0.424)比较,差异均有统计学意义(P<0.05).Na-DMPS保护组肺组织ACEmRNA表达在24 h时为0.739±0.558,3d时为0.749±0.414,ACE2 mRNA表达在3d时为0.584±0.345,7d时为0.493±0.292,明显高于相同时间点的PQ染毒组,差异均有统计学意义(P<0.05).结论 PQ中毒大鼠肺组织ACE和ACE2mRNA表达下降,Na-DMPS可上调肺组织ACE和ACE2 mRNA表达,减轻肺组织病理改变,对PQ中毒所致急性肺损伤有一定的保护作用.

Expression of angiotensin converting enzyme and angiotensin converting enzyme 2 gene in lung of paraquat poisoning rats and protection of sodium dimercaptopropane sulfonate

Objective To investigate the expression of angiotensin converting enzyme(ACE)and ACE2 Gene in lung of paraquat poisoning rats and the protection of sodium dimercaptopropane sultonate(Na-DMPS).Methods One hundred SD male rats were randomly equally divided into 4 groups:normal control grouP(10 rats),drug control group(40 rats),paraquat poisoning group(40 rats)and drug intervention group (40 rats).The paraquat poisoning and drug intervention group rats were injected intraperitoneally by paraquat (20 mg/kg).The rats in dmg intervention group rats were protected by intrapefitoneal injection with Na-DMPS (200 mg/kg)15min before exposure of paraquat.Behavioral changes of the rats and histological changes of lung tissues under light mieroscopo were observed.And the expression of ACE and ACE2 mRNA in lung tis-sues of rats both in paraquat poisoned group and drug intervention group were measured by RT-PCR at differ-ent time of 6h.24h,3 and 7d after poisoning.Results The poisoning symptoms of shortness of breath,cramps appeared and deteriorated progressively in rats after paraquat exposure and the protection of NA-DMPS could delay and reduce these symptoms significantly.Histological appearance of disorganization of pulmonary capillary and alveolus.exudation in alveolar space,pulmonary edema,severe bleeding,and intlammatory cells infiltration were obvious in lungs of rats after paraquat poisoning,whereas the histological changes were exten-uated by Drotection of NA.DMPS.As compared with normal control group(NC group),the expressions of ACE,ACE2 mRNA in lung tissue decreased,and the lowest level of ACE mRNA expressions appeared at 24 h(0.457±0.262),on 3 d(0.385±0.179)after Paraquat exposure(P<0.05),while lowest level of ACE2,RNA expressions appeared on 3 d(0.415±0.247),7 d(0.365±0.215)(P<0.05).As compared with paraquat poi-aoned group,the expressions of ACE mRNA in lung tissue of rats in NA-DM PS protected group increased sig-nificantly at24 h(0.739±0.558)and 3 d(0.749±0.414)(P<0.05),whilethe expressions of ACE2 mRNA in-creased markedly on 3 d(0.584±0.345)and 7 d(0.493±0.292)(P<0.05).Bu the expression of ACE, RNA and ACE2 mRNA in lungs had no statistical significance between normal control group and drug intenrention group(P>0.05).Conclusion The expressions of ACE and ACE2 mRNA in lung tissue of the rals with paraquat poisoning are decreased.Na-DMPS can effectively improve the balance of RAS in local lung tissue and reduce the pathological changes of lung tissue,delay the poisoning symptoms and show protective effects for acute lung injury induced by paraquat.