生脉注射液对糖尿病酮症酸中毒家兔肾功能及MMP、TIMP的影响

The Effects of Shengmai Injection on Renal Function,MMP and TIMP Proteins in Rabbits with Diabetic Ketoacidosis

目的观察生脉注射液对糖尿病酮症酸中毒(DKA)家兔肾功能及MMP、TIMP蛋白的影响。方法制备DKA模型家兔,随机分为DKA组、盐酸二甲双胍组[85 mg/(kg·d)]及生脉注射液低[3 mg/(kg/d)]、中[9 mg/(kg·d)]、高[27 mg/(kg·d)]剂量组,对照组及DKA组给予等量0.9%氯化钠注射液灌胃。连续给药7 d后,检测各组家兔动脉血电解质、血气、血酮体、血清C反应蛋白(CRP)水平及肾功能,苏木素-伊红(HE)染色观察肾组织病变,蛋白印迹(WB)检测肾组织中MMP2、TIMP2、MMP9、TIMP1表达情况。结果与对照组比较,DKA组家兔表现为DKA症状,肾功能显著下降,肾组织出现纤维化、坏死、肾小管上皮变性等病变,血清CRP水平明显增高,肾组织TIMP1、TIMP2表达明显增加,MMP2、MMP9表达显著降低(均P <0.05)。与DKA组比较,生脉注射液低、中、高剂量组治疗后,家兔DKA症状减轻,肾功能明显恢复,肾组织病变程度显著改善,血清CRP水平显著下降,肾组织TIMP1、TIMP2表达明显降低,MMP2、MMP9表达显著升高,均呈剂量依赖效应(均P <0.05)。结论生脉注射液可保护DKA家兔肾功能,其机制可能通过抑制炎症反应、调节MMP和TIMP蛋白表达实现。

Objective： To investigate the effects of Shengmai Injection on renal function,MMP and TIMP proteins in rabbits with diabetic ketoacidosis（DKA）. Methods： DKA model rabbits were prepared and randomly divided into DKA group,insulin group[85 mL/（kg·d）],low[3 mL/（kg·d）],middle[9 m L/（kg·d）] and high[27 mL/（kg·d）] dose Shengmai Injection groups. The control group and DKA group were given equal amount of 0.9%NaCl for gastric perfusion. After continuous administration for 7 d,the arterial blood electrolytes,blood gas,ketone bodies,serum CRP levels and renal function were detected in each group;HE staining was used to observe renal pathological changes;Western blotting（WB） was used to detect the expressions of MMP2,TIMP2,MMP9 and TIMP1 in renal tissues. Results： Compared with the control group,DKA group showed DKA symptoms;renal function decreased significantly;fibrosis,necrosis and degeneration of renal tubular epithelium were present in renal tissues;the level of serum CRP was significantly increased;the expressions of TIMP1 and TIMP2 in renal tissue significantly increased;the expressions of MMP2 and MMP9 decreased significantly. Compared with group DKA,after treatment,in Shengmai Injection groups,the symptoms of DKA were relieved;the renal function obviously recovered;the degree of renal tissue lesion was improved significantly;the level of serum CRP decreased significantly;the expressions of TIMP1 and TIMP2 in renal tissue decreased significantly;the expressions of MMP2 and MMP9 increased significantly. All showed dose dependent effects. Conclusion： Shengmai Injection can protect renal function of DKA rabbits,whose mechanism may be achieved by inhibiting inflammatory reaction and regulating MMP and TIMP protein expressions.