南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (04): 549-.

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硫化氢对糖尿病大鼠心肌纤维化及MAPK1/3和MMP-8表达的影响

李芳,曾欧,罗健,吴志雄,肖婷,张晶晶,杨军   

  • 出版日期:2015-04-20 发布日期:2015-04-20

Effects of hydrogen sulfide on myocardial fibrosis and MAPK1/3 and MMP-8 expression
in diabetic rats

  • Online:2015-04-20 Published:2015-04-20

摘要: 目的探讨气体信号分子硫化氢(H2S)对糖尿病大鼠心肌纤维化及MAPK1/3和MMP-8蛋白表达的影响。方法40只SD
大鼠随机分为4组:正常对照组、糖尿病大鼠组(STZ组)、硫化氢干预糖尿病大鼠组(STZ+H2S组)和硫化氢干预正常大鼠组(H2S
组)。用腹腔注射链脲佐菌素(STZ)(40 mg/kg)建立糖尿病大鼠模型;对照组每天腹腔注射生理盐水;STZ+H2S组与H2S组每天
腹腔注射硫氢化钠(H2S供体)溶液(100 μmol/kg),8周后处死大鼠,HE染色观察心肌纤维病理形态学变化,Western blot法检测
Collagen I、MAPK1/3和MMP-8蛋白的表达。结果与对照组相比,糖尿病组大鼠心肌组织胶原含量明显升高,心肌间质纤维
化,Collagen I、MAPK1/3和MMP-8蛋白表达水平显著升高(P<0.05);糖尿病大鼠经硫化氢干预后大部分心肌纤维呈平行排列,
结构清晰,间质有少量疏松结缔组织,Collagen I、MAPK1/3和MMP-8蛋白表达水平明显下调(P<0.05),而非糖尿病硫化氢干预
组心肌纤维化程度及心肌组织Collagen I、MAPK1/3和MMP-8蛋白表达水平较对照组均无明显差异(P>0.05)。结论H2S可改
善糖尿病大鼠心肌纤维化,其机制可能与抑制MAPK1/3/MMP-8信号通路有关。

Abstract: Objective To explore the effects of hydrogen sulfide (H2S) on myocardial fibrosis and expressions of MAPK1/3 and
MMP-8 in diabetic rats. Methods Forty adult male SD rats were randomized into 4 groups, namely the control group, diabetes
mellitus group (STZ group), diabetes mellitus with H2S treatment group (STZ+H2S group), and normal rats with H2S treatment
group (H2S group). Diabetes was induced by intraperitoneal injections of 40 mg/kg streptozotocin (STZ). The rats in the control
group received daily intraperitoneal injections of saline, and those in STZ+H2S group and H2S group were given NaHS (100
μmol/kg) injections. After 8 weeks, the pathologies of cardiac fibrosis were examined with HE staining, and the expressions of
collagen I, MAPK1/3 and MMP-8 were analyzed with Western blotting. Results Compared with the control group, the diabetic
rats showed increased collagen content and obvious interstitial fibrosis in the myocardial tissue with significantly increased
expression levels of collagen I, MAPK1/3 and MMP-8 (P<0.05); all these changes were obviously reversed by treatment with
H2S (P<0.05). Collagen I, MAPK1/3 and MMP-8 expression levels and the degree of myocardial fibrosis were comparable
between H2S group and control group (P>0.05). Conclusion Hydrogen sulfide can attenuate cardiac fibrosis in diabetic rats,
and the mechanism may involve the inhibition of MAPK1/3/MMP-8 signal pathway.