大豆皂苷对糖尿病大鼠心肌组织中NOX4和p22phox表达的影响及其对心肌的保护作用

［摘 要］ 目的：探讨大豆皂苷对糖尿病大鼠心肌组织中NOX4和p22phox表达的影响，阐明其对心肌的保护作用。方法：将雄性Wistar 大鼠建立糖尿病模型后随机分为糖尿病组和大豆皂苷给药组，仅注射等体积0.1 mol?L-1柠檬酸缓冲液的大鼠作为对照组，对照组、糖尿病组和大豆皂苷给药组动物分别每日灌胃给予生理盐水、生理盐水和大豆皂苷（10 mg/kg），共3个月。取心肌组织并采用实时荧光定量聚合酶链反应（PCR）测定大鼠心肌组织中NOX4和p22phox mRNA表达；免疫组织化学方法检测心肌组织中铜-锌超氧化物歧化酶（Cu-Zn-SOD）和结缔组织生长因子（CTGF）的蛋白表达；HE染色检测心肌病理学改变。结果：与对照组比较，糖尿病组大鼠心肌组织中NOX4 mRNA、p22phox mRNA和CTGF蛋白表达均显著升高（P<0.01），而Cu-Zn-SOD蛋白表达显著降低（P<0.01）；与糖尿病组比较，大豆皂苷给药组大鼠心肌组织中NOX4 mRNA、p22phox mRNA和CTGF蛋白表达均显著降低（P<0.01），但Cu-Zn-SOD蛋白表达显著增加（P<0.01）；对照组和大豆皂苷给药组上述指标比较差异均无统计学意义（P>0.05）。HE染色可见对照组大鼠心肌细胞排列紧密整齐，糖尿病组大鼠心肌细胞排列疏散紊乱，间质可见炎细胞浸润；大豆皂苷给药组大鼠心肌细胞基本整齐紧密。结论：大豆皂苷能降低糖尿病大鼠心肌组织中NOX4 mRNA、p22phox mRNA和CTGF蛋白的表达，提高Cu-Zn-SOD蛋白的表达，减轻氧化应激对心肌的损害，从而对心肌有一定的保护作用。

Effects of Soybean saponin on NOX4 and p22phox expressions in diabetic rat myocardium tissues and its protective effect on myocardium

Objective To explore the effect of Soybean saponins(SS) on the expressions of NOX4 and p22phox in the myocardium tissues of diabetic rats,and to clarify its protective effect on myocardium.Methods Male Wistar rat models of diabetes mellitus were randomly divided into diabetes group and SS treatment group,the rats in two groups were given daily saline and SS(10 mg·Kg-1)orally for 3 months;the rats treated with 0.1 mol·L-1 citrate buffer were used as control group and administrated with saline for 3 months;then the animals were killed and the myocardium tissues were obtained.The NOX4 and p22phox mRNA expressions in rat myocardium tissues were detected with real-time fluorescence quantitative polymerase chain reaction(PCR).Immunohistochemistry was used to detect the expressions of copper-zinc superoxide dismutase(Cu-Zn-SOD) and connective tissue growth factor(CTGF) in myocardium tissues.HE staining was performed to observe the pathological changes of myocardium.Results Compared with control group,the expression levels of NOX4 mRNA,p22phox mRNA and CTGF protein in myocardium tissues of rats in diabetes group were significantly increased(P<0.01),and the Cu-Zn-SOD protein expression level was significantly decreased(P<0.01).Compared with diabetes group,the expression levels of NOX4 mRNA,p22phox mRNA and CTGF protein in myocardium tissues of rats in SS treatment group were significantly reduced(P<0.01),but the Cu-Zn-SOD protein expression level was significantly increased(P<0.01);there was no significant difference of the indexes mentioned above between control group and SS treatment group(P>0.05).HE staining showed the rat myocardial cells in control group were tightly and neatly packed,but the rat myocardial cells in diabetes group arranged loosely and disorderly with infiltration of inflammatory cells in mesenchyma,and the myocardial cells in SS treatment group were also tightly and neatly packed.Conclusion SS can reduce the expression levels of NOX4 mRNA,p22phox mRNA and CTGF protein in myocardium tissues of diabetic rats,increase the expression level of Cu-Zn-SOD protein and alleviate myocardial damage induced by oxidative stress,which has a protective effect on the myocardium.