CAJ | 학술논문

目的研究长期服用辛伐他汀对机械通气肺损伤大鼠肺组织血红素加氧酶-1（HO-1）的影响。方法成年雄性清洁SD大鼠32只，体质量300～350 g，随机分4组（n＝8）：正常对照组（A组）；机械通气组（B组）；辛伐他汀组（C组）；辛伐他汀＋机械通气组（D组）。 A、B组以生理盐水1 mL/d灌胃， C、D组将辛伐他汀按10 mg/kg体质量溶于1 mL生理盐水灌胃，共灌28 d。第28天，灌胃后0．5 h，A、C组做气管切开和气管插管，自主呼吸4 h，B、D组行气管切开、插管，机械通气4 h，潮气量30 mL/kg，4 h后腹主动脉放血处死大鼠，取肺组织，分别行肺病理切片HE染色光镜下观察病理学改变，测肺湿干重比（W/D），Western blot 法检测HO-1表达， RT-PCR法检测HO-1 mRNA的表达水平。结果与A组比较， B组病理切片苏木精-伊红（HE）染色光镜下观察病理损伤改变明显加重、肺组织W/D升高（P＜0．01），HO-1和HO-1 mRNA表达水平明显升高（P＜0．01，P＜0．05），C组肺组织病理切片HE染色、肺组织W/D无明显改变， HO-1和HO-1 mRNA表达水平明显升高（ P＜0．01）；与B组比较，C组肺组织病理切片HE染色无病理改变、肺组织W/D明显降低（P＜0．01），HO-1和HO-1 mRNA表达水平比较差异无统计学意义，D组肺组织病理切片HE染色病理改变明显减轻、肺组织W/D明显降低（ P＜0.01），HO-1和HO-1 mRNA表达水平明显增高（P＜0．05，P＜0．01）；与C组比较，D组病理切片HE染色、肺组织W/D差异无统计学意义，肺组织HO-1和HO-1 mRNA表达水平明显升高（ P＜0.01）。结论长期辛伐他汀处理可以明显减弱机械通气导致的大鼠肺损伤，其机制与辛伐他汀增加肺组织HO-1和HO-1 mRNA表达水平相关。
목적연구장기복용신벌타정대궤계통기폐손상대서폐조직혈홍소가양매-1（HO-1）적영향。방법성년웅성청길SD대서32지，체질량300～350 g，수궤분4조（n＝8）：정상대조조（A조）；궤계통기조（B조）；신벌타정조（C조）；신벌타정＋궤계통기조（D조）。 A、B조이생리염수1 mL/d관위， C、D조장신벌타정안10 mg/kg체질량용우1 mL생리염수관위，공관28 d。제28천，관위후0．5 h，A、C조주기관절개화기관삽관，자주호흡4 h，B、D조행기관절개、삽관，궤계통기4 h，조기량30 mL/kg，4 h후복주동맥방혈처사대서，취폐조직，분별행폐병리절편HE염색광경하관찰병이학개변，측폐습간중비（W/D），Western blot 법검측HO-1표체， RT-PCR법검측HO-1 mRNA적표체수평。결과여A조비교， B조병리절편소목정-이홍（HE）염색광경하관찰병리손상개변명현가중、폐조직W/D승고（P＜0．01），HO-1화HO-1 mRNA표체수평명현승고（P＜0．01，P＜0．05），C조폐조직병리절편HE염색、폐조직W/D무명현개변， HO-1화HO-1 mRNA표체수평명현승고（ P＜0．01）；여B조비교，C조폐조직병리절편HE염색무병리개변、폐조직W/D명현강저（P＜0．01），HO-1화HO-1 mRNA표체수평비교차이무통계학의의，D조폐조직병리절편HE염색병리개변명현감경、폐조직W/D명현강저（ P＜0.01），HO-1화HO-1 mRNA표체수평명현증고（P＜0．05，P＜0．01）；여C조비교，D조병리절편HE염색、폐조직W/D차이무통계학의의，폐조직HO-1화HO-1 mRNA표체수평명현승고（ P＜0.01）。결론장기신벌타정처리가이명현감약궤계통기도치적대서폐손상，기궤제여신벌타정증가폐조직HO-1화HO-1 mRNA표체수평상관。
Objective To study the effects of long-term use of simvastatin on pulmonary heme oxygenase-1(HO-1) expression in rats of ventilator -induced lung injury.Methods Thirty-two SPF adult male SD rats, weighing 300~350 g were randomly divided into 4 groups ( n=8, each):control group ( group A ); mechanical ventilation group ( group B ); simvastatin group ( group C );simvastatin+mechanical ventilation group ( group D ) .Group A and B were treated with 1 mL/d of saline by gavage for 28 days;group C and D were treated with simvastatin dissolved in 1 mL saline by gavage with a dose 10 mg/kg for 28 days.Half hour after gavage on the 28th day, group A and C received tracheostomy and intubation , spontaneous breathing for 4 h; group B and D underwent tracheostomy and intubation and then received tidal volume of 30 mL/kg with mechanical ventilation for 4 h;4 h later rats were sacrificed and the lung tissue were collected and stored with correct methods .The lung tissue were performed HE staining and pathological changes were observed under light microscope . Lung wet/dry weight ratio (W/D), the expression of HO -1 mRNA and protein was detected using RT-PCR and Western blot .Results Compared with group A , group B showed significantly increased pathological damages, significantly increased W/D (P<0.01), significantly increased expression level of HO-1 protein and mRNA (P<0.01 and P<0.05, respectively).Compared with group A, group C showed no significant pathological change and W /D, but significantly increased expression level of HO-1 protein and mRNA (P <0.01).Compared with group B, group C did not show significant changes in lung pathological damage and HO -1 expression level , but the W/D was significantly reduced ( P <0.01 ) .Compared with group B , group D showed significantly decreased pathological damages, significantly reduced W/D (P <0.01), and significantly increased expression of HO -1 protein and mRNA (P <0.05 and P <0.01, respectively).Compared with group C, pathological damages and W/D in group D were not significantly difference , but the expression of HO -1 protein and mRNA were significantly increased (P<0.01).Conclusion The long -term simvastatin treatment significantly reduces lung injury caused by mechanical ventilation in rats and its mechanism is related to that simvastatin increases the expression of HO -1 protein and mRNA .