4-苯丁酸钠对大鼠糖尿病肾病的治疗作用  

Therapeutic effect of 4-phenyl butyric acid (4-PBA) as a molecular chaperone on diabetic nephropathy of rats

作　　者：齐伟[1] 牟娇[1] 叶自林[1] 郭艳红[1] 罗志锋[1] 曾薇[1] 冯兵[1] 

机构地区：[1]第三军医大学新桥医院肾内科,重庆400037

出　　处：《中国糖尿病杂志》2010年第10期781-785,共5页Chinese Journal of Diabetes

基　　金：国家自然科学基金资助项目(30570763)

摘　　要：目的观察分子伴侣4-苯丁酸钠(4-PBA)对大鼠糖尿病肾病(DN)的防治效果。方法 54只SD雄性大鼠随机分为正常对照组(NC组,n=18)、糖尿病肾病组(DN组,n=18)、4-PBA治疗糖尿病肾病组(4-PBA组,n=18)。在4周、8周、12周时分别检测大鼠肾重/体重指数(KI)、代谢参数、24h尿蛋白排泄率(UAER),观察肾脏病理改变。结果 (1)与NC组大鼠比较,DN组大鼠体重明显减轻,而肾重明显增加,相应的KI显著增大(P<0.05)。4-PBA治疗不仅使DN大鼠体重减轻程度显著减低,而且,肾重增加程度也显著降低,KI也明显下降(P<0.05)。(2)与NC组比较,DN大鼠的血糖、甘油三酯、总胆固醇、UAER均明显升高(P<0.05)。4-PBA治疗可显著降低大鼠的血糖水平,显著减少UAER(P<0.05),但对大鼠甘油三酯、总胆固醇无明显影响(P>0.05)。(3)DN大鼠肾小球基底膜增厚,系膜细胞增生、系膜基质积聚,系膜细胞和肾小管上皮细胞表达α平滑肌肌动蛋白(α-SMA)明显增多。4-PBA治疗可显著抑制上述病理改变。结论 4-PBA对大鼠DN有治疗作用。Objective To evaluate the therapeutic effect of 4-PBA on diabetic nephropathy of rats. Methods Fifty-four male Sprague-Dawley rats were randomly divided into three groups of normal control （NC, n=18）, diabetic nephropathy（DN, n= 18）, diabetic nephropathy plus 4-PBA treatment（4-PBA, n= 18）. At 4, 8 and 12 weeks, rats were sacrificed, and the kidney weight and body weight were recorded, metabolic parameters and 24h urinary albumin excretion rate （UAER）were measured, the pathological changes of kidney was detected by HE, PAS and immunohistochemical stains. Results （1） Compared with NC rats,DN group showed the decreased body weight but increased kidney weight significantly, and increased ratio of kidney weight/body weight. Treatment with 4-PBA could reverse the alteration partially （P〈0.05）. （2） Compared with NC group, the concentration of glucose（Glu）, triglyceride （TG）, total cholesterol（TC） ,and UAER increased significantly in DN group（P〈 0. 05）. The 4-PBA treatment can significantly reduce blood glucose levels and UAER in DN group. However, 4-PBA had no significant effect on the level of triglyceride, total cholesterol in rats with DN（P〉0.05）. （3） The pathological changes in rats with DN included glomerular basement membrane thickening, mesangial cell proliferation, mesangial matrix accumulation, and expression of a-smooth muscle actin （α-SMA, the representive of phenotype transformation of mesangial cells） on mesangial cells and tubular epithelial ceils. 4-PBA treatment significantly inhibited these pathological changes. Conclusions These results suggest that molecular chaperone 4-PBA could be an effective drug in treating diabetic nephropathy.

关 键 词：分子伴侣 内质网应激 糖尿病肾病 

分 类 号：R587.2[医药卫生—内分泌]