Rg1、Rb1对糖尿病肾病大鼠肾脏保护作用及其对肾组织MCP-1 mRNA与蛋白表达的影响

目的：探讨人参皂苷Rg1、Rb1对糖尿病肾病大鼠肾组织MCP-1 mRNA及蛋白表达的影响。方法：75只雄性SD大鼠,正常组10只,其余采用腹腔内一次性注射STZ55mg/kg复制糖尿病大鼠模型,造模后血糖≥16.7mmol/L,尿糖（＋＋＋＋）以上者列入实验对象。随机分为模型组、厄贝沙坦组、Rg1大剂量组、Rg1小剂量组及Rb1组,各组分别给予相应药物灌胃治疗;每周测体重,于第4、8、12周末分别留尿用考马斯亮蓝法测24h尿蛋白。12周后处死大鼠,取血清检测BUN、Scr、TG。取肾脏称重,计算肾重体重比,将肾组织固定、包埋、切片后进行HE、PAM、Mallory和Masson染色,观察大鼠肾脏病理学变化。用免疫组化、原位杂交方法分别检测肾组织MCP-1 mRNA及其蛋白的表达。结果：各治疗组大鼠体重各周与模型组比较均有所增加,但无统计学差异。与模型组比,肾重/体重,Rb1组有统计学差异（P〈0.01）,Rg1大、小剂量组有统计学差异（P〈0.05）。24h尿蛋白定量与模型组比较,4周、8周,Rg1大、小剂量组及Rb1组有统计学差异（P〈0.01）;12周,Rg1大、小剂量组及Rb1组有统计学差异（P〈0.05）。Rg1、Rb1可以见降低BUN、Scr与TG,与模型组比较,BUN均有统计学差异（P〈0.01）,Scr为Rg1大剂量组及Rb1组有统计学差异（P〈0.01）,Rg1小剂量组（P〈0.05）;TG治疗组均有降低趋势,但无统计学差异。Rg1、Rb1均可以减轻DN大鼠肾脏病理损害。同时Rg1、Rb1还可以减少肾组织MCP-1蛋白及其mRNA的表达,与模型组比较,Rg1大、小剂量组及Rb1组肾组织MCP-1蛋白的表达均显著减少,具有统计学意义（P〈0.01）,Rg1大、小剂量组及Rb1组肾组织MCP-1 mRNA表达明显减少,其中Rg1大剂量组与模型组相比有统计学意义（P〈0.05）。结论：Rg1、Rb1可以改善DN大鼠肾脏功能、减轻肾脏病理损害,其具体机制可能与下调大鼠肾组织MCP-1 mRNA及蛋白表达水平有关。

Effect of Ginsenoside-Rg1 and Rb1 on the Kidney and Renal Expression of MCP-1 mRNA and Protein in Rat Model with Diabetic Nephropathy

Objective：To investigate the effects of Ginsenoside- Rg1 and Rb1 on MCP- 1mRNA and protein expressed by rats kidney in the diabetic nephropathy （DN） model. Methods： 10 rats were assigned into normal group. Diabetes was induced in 65 SD rats by intraperitoneal injection of streptozotocin （STZ） in diabetic group. The rats with blood glucose over 16.7 mmol/l and urinary glucose over （ ＋ ＋ ＋ ＋ ） were recognized as DM animal model. The urine was collected respectively at the end of the 4th, the 8th and 12th week,and 24- hour urinary protein （LIP） were determined by coomassie briliant blue method. At the 12th week, all the rats were sacrificed, and the serum was collected for determination of blood urea nitrogen （BUN）, serttm creatinine （Scr） and Triglyceride （TG）. Kidney was taken for pathological examination （HE, PAM, Mallory and Masson stain）. In situ Hybridization and immunohistochemistry were adopted to examine the expression of MCP - 1mRNA and protein in the kidney. Results： Compared with model group, the body weight increased in all the treatment groups, but there was no significant difference; the weight ratio of kidney/boody in Rb1 group was significantly decreased （ P 〈 0.01 ） ; the weight ratio of kidney/body in Rg1 high does group and low dose group were also decreased （P〈0.05）;the LIP of Rg1 high dose group and Rg1 low dose group were significantly decreased （P〈 0.01） at the end of the 4th and the 8th week,and that in the Rb1 group was also decreased （P〈0.05） at the end of the 12 week. Compared with model group, the BUN of all the other groups were significantly decreased （ P 〈 0.01 ） ;Ser levels in the Rg1 high dose and the Rb1 group were significantly decreased （P 〈 0.01 ）, and the same was true in the Rg1 low dose group （P 〈 0.05） ; TG levels of all the other group were decreased, but there was no significant difference. Severe pathological changes of kidney structure in the rats were observed to be relieved with the