硫化氢对油酸诱导急性肺损伤大鼠细胞外基质的调节作用

硫化氢对油酸诱导急性肺损伤大鼠细胞外基质的调节作用
刘妍;王海英;刘文莉;吴昊;李瑞明;陈志芳;赵斌
【期刊名称】《中国急救医学》
【年(卷),期】2011(031)009
【摘要】目的探讨外源性硫化氢(H2S)对油酸诱导的急性肺损伤(ALI)大鼠细胞外
基质(ECM)的调节作用.方法雄性SD大鼠35只,随机分为对照组(n=5)、油酸组(n=15)、油酸+硫氢化钠(NaHS)组(n=15).油酸组大鼠尾静脉注射油酸0.1 mL/kg;油酸+NaHS组先腹腔注射NaHS 56 μmol/kg(溶于0.5 mL生理盐水中),30 min
后再尾静脉注射油酸0.1 mL/kg.以上两组均分为2、4、6 h三个观察点,每个点5只.对照组大鼠尾静脉注射0.1 mL/kg生理盐水,观察6 h.在观察时间结束后,麻醉大鼠,行支气管肺泡灌洗,灌洗液(BALF)沉渣行瑞士染色进行中性粒细胞(PMN)分类计数;取右肺上叶,计算湿重/干重(W/D)值;用ELISA法检测血浆、肺组织匀浆基质金
属蛋白酶-9(MMP-9)、组织金属蛋白酶抑制剂-1(TIMP-1)水平;用敏感硫电极法检测H2S水平.结果与对照组比较,油酸组2、4、6 h PMN显著升高(P均<0.01);与油酸组比较,油酸+NaHS组各时间点PMN显著降低(P均<0.05).与对照组比较,油酸组2、4、6 h肺W/D值显著升高(P均<0.01);与油酸组比较,油酸+NaHS组4、6 h肺W/D值显著降低(P均<0.05).与对照组比较,油酸组2、4、6 h血浆、肺组
织匀浆H2S水平显著降低(P均<0.01);与油酸组比较,油酸+NaHS组血浆、肺组织匀浆H2S水平4、6 h显著升高(P均<0.05).与对照组比较,油酸组2、4 h血浆、
肺组织匀浆及6 h血浆MMP-9水平显著升高(P均<0.05);与油酸组比较,油酸
+NaHS组4 h 血浆MMP-9水平显著降低(P<0.05),2、6 h血浆、肺组织匀浆及
4 h 肺组织匀浆MMP-9水平降低,但差异无统计学意义(P均>0.05).与对照组比较,
油酸组4 h 血浆、肺组织匀浆及6 h肺组织匀浆TIMP-1水平显著降低(P均
<0.05);与油酸组比较,油酸+NaHS组2、4、6 h血浆、肺组织匀浆TIMP-1水平升高,但差异无统计学意义(P均>0.05).结论外源性H2S可能通过调节肺组织MMP-9和TIMP-1水平的变化,发挥对油酸诱导大鼠ALI 的细胞外基质的调节作用.%Objective To explore the regulative effects of hydrogen sulfide (H2S) on extracellular matrix(ECM) in acute lung injury(ALI) rats induced by oleic acid(OA). Methods Thirty - five male SD rats were randomly divided into control group ( n= 5 ), OA group ( n= 15 ) and OA + sodium hydrosulfide (NaHS) group(n= 15). ALI was induced by injecting oleic acid (0.1 mL/kg) intravenously as OA group; controls were given normal saline (0. 1 mL/kg); NaHS solution (56 μ mol/kg) was inject ed intra -peritoneally 30 minutes before OA injection (0.1 mL/kg) as OA + NaHS group. OA group and OA + NaHS group were executed at 6 h after the administration of
OA,respectively. Control group was executed at 6 hours after receiving intravenous normal saline. The measured indexes included counts of polymorphonuclear (PMN) in BALF and wet weight/dry weight (W/D) ratio. The concentrations of H2S and the levels of matrix metalloproteinase -9 (MMP -9),tissue inhibitor of metalloproteinase - 1 ( TIMP - 1 ) in the plasma and lung tissue were detected respectively. Results Compared with control group, the percentage of PMN cells in the BALF were significantly increased in rats treated with OA at each time point ( all P ＜0.01 ). The lung W/D ratio was also significantly higher in OA - treated rats than controls at each time point ( all P ＜ 0. 01 ).Compared with OA group, the percentage of PMN cells in the BALF lowered at each time point (all P
＜0.05 ) and W/D ratio in the lung tissue decreased at 4, 6 h ( all P ＜ 0.05 ) in OA + NaHS group. H2 S levels in both the plasma and lung tissue of OA - treated rats were significantly lower than those of controls at each time point (all P ＜ 0.01 ), NaHS significantly increased H2S levels in the plasma and lung tissue compared with the OA - alone group at 4, 6 h ( all P ＜
0.05). Compared with control group,MMP - 9 levels were significantly increased at 2, 4 h in both the plasma and lung tissue and at 6 h in the plasma of the OA - treated rats. TIMP - 1 levels was significantly lower at 4 h in both the plasma and lung tissue and at 6 h in the lung tissue of OA -treated rats (all P ＜ 0.05). Administration of the H2 S donor in the OA - treated rats significantly decreased the MMP - 9 levels in the plasma at 4 hour compared with the OA - alone group (P ＜ 0.05 ). Conclusion Exogenous H2S could regulate the changes of MMP - 9 and TIMP - 1 levels in lung tissue during ALI and play the regulative effect on extracellular matrix in ALI rats induced by OA.
【总页数】5页(P826-830)
【作者】刘妍;王海英;刘文莉;吴昊;李瑞明;陈志芳;赵斌
【作者单位】100035,北京积水潭医院急诊科;100035,北京积水潭医院急诊
科;100035,北京积水潭医院急诊科;100035,北京积水潭医院急诊科;100035,北京积水潭医院急诊科;100035,北京积水潭医院急诊科;100035,北京积水潭医院急诊科【正文语种】中文
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