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目的:观察维生素C对糖尿病肾病大鼠Ⅳ型胶原α1mRNA表达及肾脏功能的影响。方法:实验于2004-01/04在南华大学动物部完成。大鼠预养1周后,空腹12h,腹腔注射60mg/kg链尿佐菌素-柠檬酸钠缓冲液,对照组注射等量柠檬酸钠缓冲液,依据72h后尿糖～,静脉采血测血糖≥16.7mmol/L,确定建立Ⅰ型糖尿病大鼠模型。将SD大鼠随机分为正常对照组、糖尿病组和维生素C组,保持大鼠血糖波动在25mmol/L左右,持续16周。观察治疗期间及治疗后大鼠的一般状况、血糖、尿素氮、血肌酐,内生肌酐清除率、24h尿蛋白排泄率,原位杂交检测肾组织Ⅳ型胶原α1基因表达。结果:30只SD大鼠实验过程中无死亡,全部纳入结果分析。①大鼠体质量较正常对照组明显下降,尿量增加,血糖升高,差异有显著性意义(t=4.945,3.779,P<0.05),治疗后维生素C组与糖尿病组相比,体质量、肾质量/体质量有显著提高(t=2.927,3.032,P<0.05)。②大鼠血清尿白蛋白排泄率、血肌酐、尿素氮较正常对照组明显升高,内生肌酐清除率下降,有显著性差异(t=4.113,3.1251,2.798,P<0.05),糖尿病组与维生素C组相比,尿白蛋白排泄率、血肌酐、尿素氮明显升高,内生肌酐清除率下降(t=2.875,2.994,3.102,P<0.05)。③与正常对照组相比,肾小球血管细胞外基质Ⅳ型胶原α1基因表达显著上调,经灰度值测定两组间差异有显著性意义(P<0.05,t=4.766),治疗后维生素C组肾组织着色浅淡稀疏,与糖尿病组相比Ⅳ型胶原α1基因相对表达明显下调(t=2.879,P<0.05)。结论:维生素C无降糖作用,但具有确切的肾脏保护作用。
Objective: To observe the effect of vitamin C on the expression of type Ⅳ collagen α1 and renal function in rats with diabetic nephropathy. Methods: The experiment was performed at Animal Department of Nanhua University from January to April 2004. Rats were pre-nourished for 1 week, fasting 12h, intraperitoneal injection of 60mg / kg streptozotocin-sodium citrate buffer, the control group was injected sodium citrate buffer equivalent, according to 72h urine ~, venous blood glucose ≥16.7mmol / L, to establish a type 1 diabetic rat model. SD rats were randomly divided into normal control group, diabetic group and vitamin C group, to maintain blood glucose in rats fluctuated at 25mmol / L for 16 weeks. The general condition, blood glucose, urea nitrogen, serum creatinine, endogenous creatinine clearance rate and urinary protein excretion rate during and after treatment were observed. The expression of type Ⅳ collagen α1 gene in renal tissue was detected by in situ hybridization. Results: Thirty SD rats died without any experiment and all were included in the result analysis. Compared with the normal control group, the body weight of rats decreased significantly, urine output increased and blood glucose increased, the difference was significant (t = 4.945, 3.779, P <0.05) , Kidney mass / body weight was significantly increased (t = 2.927, 3.032, P <0.05). ② Serum urinary albumin excretion rate, serum creatinine and urea nitrogen were significantly higher than those in normal control group and endogenous creatinine clearance rate was significantly decreased (t = 4.113, 3.1251, 2.798, P <0.05) Compared with vitamin C group, urinary albumin excretion rate, serum creatinine and urea nitrogen were significantly increased, endogenous creatinine clearance rate decreased (t = 2.875,2.994,3.102, P <0.05). ③Compared with the normal control group, the expression of collagen Ⅳ gene in glomerular extracellular matrix was significantly up-regulated (P <0.05, t = 4.766) Compared with diabetic group, the expression of type Ⅳ collagen α1 gene was significantly down-regulated in group C (t = 2.879, P <0.05). Conclusion: Vitamin C has no hypoglycemic effect, but has definite renal protective effect.