外源性硫化氢减轻D－半乳糖诱导的亚急性衰老大鼠心肌纤维化  

Exogenous hydrogen sulfide reduces D-galactose induced myocardial fibrosis in subacute aging rats

作　　者：黄继良[1,2] 刘磊[1] 乔伟丽[1] 夏勇[2] 闫长栋[1] 

机构地区：[1]徐州医学院生理学教研室,江苏徐州221004 [2]徐州医学院心血管病研究所,江苏徐州221004

出　　处：《徐州医学院学报》2016年第1期17-20,共4页Acta Academiae Medicinae Xuzhou

基　　金：国家自然科学基金（81200250）;江苏省自然科学基金（BK20131119）

摘　　要：目的：观察硫化氢（ H2 S）处理对亚急性衰老大鼠心肌纤维化的影响。方法健康雄性SD大鼠随机分为3组，每组6只。对照组每日背部皮下和腹腔注射等体积生理盐水；D－半乳糖组每日背部皮下注射D－半乳糖（125 mg· kg^-1· d^-1），同时腹腔注射等体积生理盐水；硫氢化钠（NaHS，H2S供体）组每日背部皮下注射D－半乳糖（125 mg·kg^-1· d^-1），同时腹腔注射NaHS（10μmol· kg^-1· d^-1）。每组处理时间均为8周。苏木精－伊红染色和Masson染色观察大鼠心肌细胞和心肌胶原纤维等形态学变化；免疫印迹法测定大鼠心肌基质金属蛋白酶2（MMP－2）及基质金属蛋白酶抑制剂－1（TIMP－1）蛋白的表达。结果与对照组相比，D－半乳糖组大鼠心重指数增高（P＜0．01），心肌胶原纤维容积率增加（P＜0．05），心肌组织MMP－2表达减少（P＜0．01），TIMP－1表达增加（P＜0．01）。与D－半乳糖组相比，NaHS组大鼠心重指数降低（P＜0．05），心肌胶原纤维容积率减少（P＜0．05），心肌MMP－2表达增加（P＜0．05），TIMP－1表达减少（P＜0．01）。结论外源性H2S处理可以促进心肌胶原纤维降解，抑制胶原纤维聚集，从而减少D－半乳糖诱导的亚急性衰老大鼠心肌纤维化，其机制可能是通过减少TIMP－1蛋白的表达，增加MMP－2的活性，调节MMP－2／TIMP－1的平衡实现。Objective To investigate the effects of exogenous hydrogen sulfide （ H2 S） on D-galactose-induced myocardial fibrosis in subacute aging rats .Methods Healthy male SD rats were randomly divided to three groups （ n=6 each）：a control group, a D-galactose （D-gal） group and a sodium hydrogen sulfide （NaHS） treatment group.The control group was subcutaneously and intraperitoneally injected with the same volume of normal saline per day .The D-gal group was subcutaneously injected with 125 mg/kg of D-galactose and intraperitoneally injected with the same vol-ume of normal saline per day .The NaHS treatment group was subcutaneously injected with 125 mg/kg of D-galactose and intraperitoneally injected with 10 μmol/kg NaHS per day.All groups were treated for eight weeks .Then, the mor-phological changes of cardiomyocytes and collagen fibers in cardiac muscles were observed by H -E and Masson staining . The amounts of matrix metalloproteinase （ MMP-2 ） and tissue inhibitor of metalloproteinase （ TIMP -1 ） in cardiac muscles were determined by Western blotting .Results Compared with the control , the D-gal group showed increases in cardiac index （P〈0.01）, myocardial collagen fiber volume fraction （P〈0.05） and TIMP-1 level （P〈0.01）, and decrease in MMP-2 level （P〈0.01）.Compared with rats treated with D -gal alone, those receiving both NaHS and D-gal presented decreases in cardiac index （P〈0.05）, myocardial collagen fiber volume fraction （P〈0.05） and TIMP-1 level （P〈0.05）, as well as increases in MMP-2 level （P〈0.01）.Conclusion Exogenous H2S can stim-ulate the decomposition of myocardial collagen fibers and inhibit the aggregation of the fibers , in order to relieve D-ga-lactose-induced myocardial fibrosis in subacute aging rats , which may be associated with reduced levels of TIMP -1 , enhanced activity of MMP -2 and a well balanced ratio of MMP -2/TIMP-1.

关 键 词：硫化氢 衰老 心肌纤维化 基质金属蛋白酶-2 基质金属蛋白酶抑制剂-1 

分 类 号：R285.5[医药卫生—中药学]