藕节对糖尿病肾病大鼠肾组织JAK2/STAT3及凋亡因子表达的影响

Effect of Rhizoma Nelumbinis on JAK2/STAT3 and Apoptosis Factors in Diabetic Nephropathy Rats

目的:探讨藕节对糖尿病肾病大鼠肾组织p-JAK2、p-STAT3及凋亡因子Bcl-2、Bax表达的影响。方法:健康雄性SD大鼠60只,随机选取10只为正常组(N组),其余采用单次腹腔注射链尿佐菌素(STZ,45 mg/kg)制作DN模型,造模成功后随机分为糖尿病肾病组(DN)、藕节小剂量组(RL,1.5 g·kg-1·d-1)、中剂量组(RM,3.0 g·kg-1·d-1)、大剂量组(RH,6.0 g·kg-1·d-1)及氯沙坦钾组(LP,30 mg·kg-1·d-1),均采用灌胃给药,N组和DN组给予等量蒸馏水。12周后检测大鼠生化指标;HE、Masson染色及电镜观察肾脏病理改变;免疫组化法测定p-JAK2、p-STAT3、Bcl-2及Bax在肾组织表达情况;原位末端标记法(TUNEL)检测肾组织细胞凋亡情况。结果:实验12周末,与N组比较,DN组大鼠肾小球肥大、系膜基质增多、细胞凋亡明显,BUN、Scr、24 h尿蛋白定量明显升高(P<0.05),肾组织Bax、p-JAK2、p-STAT3表达明显上调,Bcl-2表达下调(P<0.05);与DN组比较,藕节中、高剂量组肾脏病理改变减轻、细胞凋亡减少,24 h尿蛋白定量较DN组明显降低(P<0.05),但降尿蛋白作用弱于氯沙坦钾组,同时肾组织Bax、p-JAK2、p-STAT3表达下调,Bcl-2表达上调(P<0.05)。结论:藕节可能通过上调Bcl-2在肾组织的表达,下调Bax、p-JAK2、p-STAT3的表达,从而减少尿蛋白,延缓DN进展。

Objective：To investigate the effect of Rhizoma Nelumbinis on expression of p-JAK2,p-STAT3,Bcl-2 and Bax in renal tissues of diabetic nephropathy rats. Methods：60 SD male rats were randomly divided into 6 groups：the normal control group（group N）,diabetic nephropathic model group（group DN）,low-dose Rhizoma Nelumbinis group （RL,1. 5 g·kg-1·d-1）, medium-dose Rhizoma Nelumbinis group（RM,3. 0 g·kg-1·d-1）,high-dose Rhizoma Nelumbinis group（RH,6. 0 g·kg-1· d-1 ） and losartan potassium group （ LP, 30 mg · kg-1 · d-1 ） . Rats were treated respectively by intragastric administration for 12 weeks. Meanwhile rats of group N and group DN received the same volume distilled water by gavage. Blood serum creatinine,blood urea nitrogen and 24 h urinary protein were measured after the research. The renal pathological changes were observed by histochemis-try staining and electron microscope. The expression of p-JAK2,p-STAT3,Bcl-2 and Bax were detected by immunohistochemis-try. The cell apoptosis was detected by TUNEL. Results：Compared with group N,the glomerular became hypertrophic and the mesang-ial matrix increased in group DN. BUN,Scr,24 h urinary protein also increased significantly （P〈0. 05）. Meanwhile the expression of Bax,p-JAK2,p-STAT3 in renal tissue increased,the expression of Bcl-2 decreased significantly（P〈0. 05）. Compared with group DN,group RM and group RH had significantly lower 24 h urinary protein （P〈0. 05）,the pathology changes were relieved,cell apop-tosis was reduced,and the expression of Bax,p-JAK2,p-STAT3 decreased and the expression of Bcl-2 increased （P〈0. 05）. In addition,the effect of reducing urinary protein in group RM,RH was less than those of group LP. Conclusion：Rhizoma Nelumbinis may reducing urinary protein and delay the injury in diabetic nephropathy by down-regulating the level of Bax,p-JAK2,p-STAT3, up-regulating the level of Bcl-2.