CTX对2型糖尿病肾病的治疗作用

Therapeutic effect of cyclophosphamide on type 2 diabetic nephropathy in rats

目的探讨环磷酰胺(CTX)对2型糖尿病肾病大鼠蛋白尿的治疗作用。方法 80只SD雄性大鼠随机分为对照组(N组,n=14)、高脂饮食组(HF组,n=66)。HF组给予高脂饲料8周,产生胰岛素抵抗后,一次性腹腔注射STZ(35 mg/kg),对照组给予常规饲料,腹腔注射等量的柠檬酸-柠檬酸钠缓冲液。2型糖尿病肾病造模成功后,又将成模大鼠随机分为2型糖尿病肾病模型组(DN组,n=18)及治疗组(CTX组,n=36)。CTX组腹腔注射给予环磷酰胺(CTX)30 mg/kg,N组及DN组给予等量的生理盐水腹腔注射。两组均为每周一次,连续4周。测三组大鼠24 h尿蛋白定量,心脏取血测尿素氮(BUN)、肌酐(Scr),计算肾脏肥大指数(KHI),光镜下观察肾脏病理改变。结果①腹腔注射STZ后14 d,HF组与N组血糖、尿蛋白定量比较,差异有统计学意义(P<0.01);②环磷酰胺治疗4周后疗效比较,尿蛋白定量在N组、DN组、CTX组的中位数分别是13.08 mg/24 h、54.19 mg/24 h、43.30 mg/24 h,三组差异有统计学意义(P<0.01);③DN组尿素氮及肌酐较其他两组高,CTX组的尿素氮高于N组,差异有统计学意义(P<0.05),肌酐在CTX组与N组间差异无统计学意义(P>0.05);④DN组表现有肾小球系膜细胞增生,基底膜增厚,间质有炎性细胞浸润,间质纤维化,CTX组上述病理改变较DN组明显减轻,但较N组明显。结论环磷酰胺能够减少2型糖尿病肾病大鼠的蛋白尿、能减轻肾功能损害并能使病理改变减轻。

Objective To explore the therapeutic action of eyclophosphamide （CTX） on proteinufia in rats with type 2 diabetic ne- phropathy. Methods Eighty male SD rats were randomly divided into normal group （n = 14） and high-fat group （n = 66 ）. Rats in high-fat group were given high-fat diet for 8 weeks ,and they were intraperitoneally injected with low-dose of STZ （35 mg/kg） after in- sulin resistance ; while the rats in normal group were given the routine diet and injected with the same volume of citric acid-citrate sodi- um buffer. After type 2 diabetic nephropathy model was established successfully, DN rats were divided into two groups：DN group（ n = 18） and medication group （CTX group,n =36）. The rats were given CTX 30 mg/kg in CTX group and the same amount of physiologi- eal saline in the other two groups once a week for 4 weeks. Then 24 h urine protein, BUN and Scr in three groups were detected, kidney hypertrophy index was calculated, and renal pathology was observed under light mieroseope. Results （1）At 14 d after injected with STZ, the levels of blood sugar and urinary albumen were different between high-fat group and normal group （ P 〈 0.01 ）. （2）After admin- istrating CTX for 4 weeks ,median of urinary albumen was 13.08 mg/24 h ,54.19 mg/24 h,43.30 mg/24 h in normal group, DN group and CTX group, respectively, and there was significant difference among three groups. （3）The levels of BUN and Ser were significantly higher in DN group than those in the other two groups （P 〈 0. 05 ）. The level of BUN in CTX group was signifieantly higher than in nor- real group（P 〈0.05 ） ,but there was no difference in Scr between CTX group and normal group（P 〉 0.05 ）. （4）Renal pathology showed glomerular mesangial eell proliferation,basement-membrane thiekening, inflammatory cell invasion and renal interstitial fibrosis in DN group. The pathological changes were signifieanfly alleviated in CTX group, but were severer than in normal group. Conclusion CTX can decrease the proteinuria and lighten the injury of renal function in rats with type 2 diabetic nephropathy.