人参皂甙Rg3对糖尿病肾病大鼠肾组织Bax和B淋巴细胞瘤-2蛋白表达及肾细胞凋亡的影响

目的探讨糖尿病肾病(diabetic nephropathy,DN)大鼠应用人参皂甙Rg3处理后肾组织Bax、B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)蛋白表达变化及肾细胞凋亡情况。方法120只雄性SD大鼠,随机分为模型组、治疗组和对照组各40只。模型组、治疗组腹腔注射质量分数2%链尿佐菌素溶液制备DN模型,对照组腹腔注射等量生理盐水。造模成功后,治疗组将0.5 mg/kg人参皂甙Rg3与生理盐水混合溶液灌胃,模型组、对照组大鼠给予等量生理盐水灌胃,均1次/d,连续28 d。疗程结束后大鼠麻醉处死,取肾组织行病理检查,采用TUNEL法检测肾组织细胞凋亡,Western blot法检测肾组织Bax、Bcl-2蛋白相对表达量,实时荧光定量PCR法检测肾组织Bax mRNA、Bcl-2 mRNA相对表达量。结果对照组大鼠肾组织系膜结构、肾小管均正常,小管膜完整光滑,间质未增生;模型组大鼠肾组织系膜结构异常,间质严重增生,肾小管萎缩严重,小管膜粗糙;与模型组比较,治疗组大鼠肾组织系膜细胞增生减轻,肾小管萎缩减少,纤维组织减少;模型组、治疗组、对照组大鼠肾细胞凋亡率[(0.91±0.23)%、(0.56±0.14)%、(0.21±0.03)%]依次降低(P<0.05);模型组、治疗组、对照组肾组织Bax蛋白相对表达量(1.79±0.31、2.73±0.24、3.26±0.12)、Bcl-2蛋白相对表达量(1.42±0.12、2.59±0.25、4.40±0.31)、Bax mRNA相对表达量(0.35±0.02、1.45±0.91、3.12±1.17)、Bcl-2 mRNA相对表达量(1.34±0.87、1.73±0.67、3.91±0.75)依次增高(P<0.05)。结论人参皂甙Rg3对DN大鼠有显著治疗作用,可明显改善大鼠肾组织形态,降低肾细胞凋亡率,上调Bax、Bcl-2表达。

Influence of ginsenoside Rg3 on the expressions of Bax and B-cell lymphoma-2 protein and renal cell apoptosis in rats with diabetic nephropathy

Objective To investigate the expressions of Bax and B-cell lymphoma-2(Bcl-2)treated with ginsenoside Rg3 and renal cell apoptosis in rats with diabetic nephropathy(DN).Methods Totally 120 male rats were randomly divided into model group,treatment group and control group,with 40 rats in each group.Model group and treatment group were injected with 2%streptozotocin to prepare DN models,while control group was intraperitoneally injected with the same amount of normal saline.After successful modeling,treatment group received lavage with mixed solution of ginsenoside Rg3 and normal saline,0.5 mg/kg,while model group and control group received lavage with the same amount of normal saline,once a day,totally for 28 days.All rats were anesthetized and sacrificed to obtain the renal tissue for histopathological examination.TUNEL method was used to detect the apoptosis of the renal cells.Western blot was used to detect the relative expressions of Bax and Bcl-2 protein.Real-time fluorescence quantitative PCR was used to detect the relative expressions of Bax mRNA and Bcl-2 mRNA.Results The histopathological examination showed normal mesangial structure and renal tubules,intact tubule membrane and no interstitial hyperplasia in control group;abnormal renal mesangial structure,severe interstitial hyperplasia,tubule atrophy and rough tubule membrane in model group;reduced mesangial hyperplasia,tubular atrophy and fibrosis in treatment group compared with model group.The apoptotic rate of renal cells reduced gradually in turn in model group,treatment group and control group(0.91±0.23,0.56±0.14,0.21±0.03)(P<0.05).The relative expressions of Bax protein(1.79±0.31,2.73±0.24,3.26±0.12),Bcl-2 protein(1.42±0.12,2.59±0.25,4.40±0.31),Bax mRNA(0.35±0.02,1.45±0.91,3.12±1.17)and Bcl-2 mRNA(1.34±0.87,1.73±0.67,3.91±0.75)increased gradually in turn in model group,treatment group and control group(P<0.05).Conclusion Ginsenoside Rg3 has a remarkable effect on DN rats by improving the kidney morphology,reducing the apoptotic rate and up-regulating the expressions of Bax and Bcl-2.