参附注射液对大鼠肠缺血再灌注致急性肺损伤的影响

Influence of Shenfu Injection on Acute Lung Injury Induced by Intestinal Ischemia Reperfusion of Rats

目的:观察参附注射液对大鼠肠缺血再灌注致急性肺损伤的影响。方法:建立肠缺血再灌注致急性肺损伤模型,将造模成功的40只大鼠随机分为对照组(C组)、缺血再灌注组(I/R组)、参附后处理组(SFPO组)、血晶素组(Hemin组)、锌原卟啉IX+SFPO组(Zn PPIX+SFPO组),每组各8只。C组分离肠系膜上动脉但不阻断;I/R组肠系膜上动脉阻断1 h后再灌注2 h,股静脉恒速泵入等量生理盐水;SFPO组肠系膜上动脉阻断1 h后将10 m L·kg-1的参附注射液从股静脉恒速泵入;Hemin组肠系膜上动脉阻断前24 h腹腔注射Hemin 75μmol·kg-1;ZnPPIX+SFPO组肠系膜上动脉阻断前24 h腹腔注射锌原卟啉IX(20 mg·kg-1),后续操作同SFPO组。术前无需给药的各组腹腔注射等剂量的生理盐水,于再灌注2 h后颈动脉放血处死动物。观察各组大鼠肺组织中血红素加氧酶1(HO-1)的表达,丙二醛(malonaldehyde,MDA)、超氧化物歧化酶(Superoxide Dismutase,SOD)含量和肺通透性指数、动脉血气和肺组织湿/干质量比值的影响。结果:与I/R组比较,SFPO组和Heim组肺组织HO-1表达增高;Zn PPIX+SFPO组表达降低(P<0.05)。SFPO组和Heim组肺组织湿/干质量比、MDA和通透性指数均显著降低,而SOD值明显升高(P<0.05或P<0.01);与C组比较,缺血再灌注组肺组织湿/干质量比、MDA和通透性指数均明显增高,而SOD显著降低(P<0.05);与C组比较,各组动物动脉血PaO_2、PaCO_2显著下降(P<0.05),与I/R组比较,SFPO组和Heim组PaO_2、PaCO_2明显增高,差异具有统计学意义(P<0.05)。结论:参附注射液可能通过直接诱导血红素加氧酶-1蛋白表达、一定程度上抑制脂质过氧化、拮抗氧自由基的损伤,提高抗氧化能力,改善肺部微循环,发挥IIR损伤所致的急性肺损伤的保护作用。

Objective ： To observe the influence of Shenfu Injection on acute lung injury, induced by intestinal ischemia reperfusion of rats. Methods： Model rats with acute lung injury induced by intestinal isehemia reperfusion were established, and the 40 suc- cessfully established model rats were randomized into control group （group C ） , ischemia reperfusion group （group I/R ）, Shenfu Post-management group （group SFPO）, group Heroin and group Zn-protoporphyrinIX ＋ SFPO（ group ZnPPIX ＋ SFPO ）, with 8 rats in each group. Group C were conducted separation of the superior mesenteric artery without blocking; group 1/R were con- ducted separation of the superior mesenterie artery and after lh reperfusion was performed for 2 h, and the femoral veins were pumped same amount of normal saline with constant speed; group SFPO were conducted separation of the superior mesenteric ar- tery. and after l h Shenfu Injection of 10 mL · kg-1 was pumped along the femoral vein in constant speed; Group Heroin were con- ducted intraperitoneal injection of Hemin 75 μmol · kg-1 and after 24 h performed separation of the superior mesenteric artery; group ZnPPIX ＋ SFPO were conducted intraperitoneal injection of IX （ 20 mg · kg - 1 ） and after 24 h performed separation of the superior mesenteric artery, the following manipulation being the same as that of group SFPO. Groups without administration were conducted intraperitoneal injection of same amount of normal saline and after 2 h of reperfusion the rats were executed by bloodlet- ting of the carotid artery. The expression of HO-A in the lungs of rats in each group and the content of MDA, SOD as well as the influence on the permeability of the lung, the arterial blood gases, and ratio of wet to dry mass of the lung were observed. Re- suits ： Compared with group I/R, the expression of HO-1 in group SFPO and group Heim increased; the expression in group Zn- PPIX ＋ SFPO declined （P 〈0.05）; the wet/dry mass ratio, MDA and permeability index in group SFPO and group Heim re- markably decreased while the value of SOD increased obviously （ P 〈 0. 05 or P 〈 0. 01 ） ; compared with group C, the wet/dry mass ratio, MDA and permeability index in group I/R group apparently increased but the value of SOD decreased markedly （P 〈 0.05 ）. Compared with group C, the levels of PaO2 and PaCO2 in each group declined greatly （ P 〈 0.05 ）. Compared with group I/R, the levels of PaO2 and PaCO2 in group SFPO and group Heim increased obviously ; the difference had statistical significance （P 〈0.05 ）. Conclusion： By directly inducing the expression of HO-1, Shenfu Injection inhibit the lipid peroxidation and injury of the antagonism of oxygen free radicals, enhance the oxidation resistance, improve lung miecmcirculation and exert protective effect on the acute lung injury induced by IIR injury.