糖基化终末产物影响结肠平滑肌肌球蛋白轻链激酶表达在糖尿病大鼠结肠动力障碍中的作用  

Effect of advanced glycation end products on myosin light chain kinase expression in smooth muscle cells and colonic motility dysfunction in diabetic rats

作　　者：王庆娥[1] 王云[1] 朱滢[1] 孙晓萌[1] 林琳[1] 

机构地区：[1]南京医科大学第一附属医院消化科,江苏省南京市210029

出　　处：《世界华人消化杂志》2014年第17期2427-2433,共7页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81270462;江苏省国际合作基金资助项目;No.BZ2011044~~

摘　　要：目的:探讨糖基化终末产物(advanced glycation e n d p r o d u c t s,A G E s)对糖尿病(d i a b e t e s mellitus,DM)大鼠结肠动力及肌球蛋白轻链激酶(myosin light chain kinase,MLCK)表达的影响.方法:SD大鼠48只,随机均分为4组,即正常对照组、正常+AGEs抑制剂氨基胍(a m i n o g u a n i d i n e,A G)干预组、D M组、D M+A G干预组.单次腹腔注射链脲佐菌素(streptozotocin,STZ)(60 mg/kg)构建DM大鼠模型,造模成功后,AG干预按1 g/L饮用水给药,持续至实验结束.ELISA、Western blot检测大鼠血清及结肠肌层AGEs水平,玻璃珠排出法检测结肠转运功能,MPA分析系统检测结肠环肌肌条收缩力,Western blot检测结肠肌层肌球蛋白轻链激酶(myosin light chain kinase,MLCK)的表达.各组间比较采用单因素方差分析和成组t检验.结果:与正常对照组相比,DM大鼠结肠肌层AGEs表达增多,血清AGEs水平升高(3.00μg/mL±0.34μg/mL vs 4.31μg/mL±0.73μg/mL,P<0.01),结肠转运时间延长(209.50min±48.88 min vs 297.00 min±35.71 min,P<0.01),环肌肌条收缩力减弱(2.17 g±0.57g vs 0.80 g±0.34 g,P<0.01),结肠肌层MLCK蛋白表达减少(1.46±0.11 vs 1.01±0.08,P<0.01).AG干预不影响大鼠血糖水平,但与DM组相比,DM+AG组大鼠结肠AGEs表达减少,血清AGEs水平降低(4.31μg/mL±0.73μg/mL vs 3.35μg/mL±0.58μg/mL,P<0.05),结肠转运时间缩短(297.00 min±35.71 min vs 212.13min±42.95 min,P<0.01)、肌条收缩力增强(0.80 g±0.34 g vs 1.49 g±0.44 g,P<0.01),结肠肌层MLCK蛋白表达升高(1.01±0.08 vs1.40±0.09,P<0.01).结论:AGEs可能通过减少结肠肌层MLCK蛋白表达参与DM大鼠结肠动力障碍的发生.AIM： To investigate whether advanced glycation end products （AGEs） affect colonic motility and the expression of myosin light chain kinase in diabetic rats. METHODS： Fortyeight SD rats were evenly and randomly divided into four groups： normal controls, normal rats treated with aminoguanidine（AG, an inhibitor of AGEs）, diabetic rats, and diabetic rats treated with AG. Diabetes mellitus （DM） was induced by a single intraperitoneal injection of streptozotocin （STZ） （60 mg/kg）. AG was given in drinking water at a dose of 1 g/L after DM was induced. ELISA and Western blot were used to measure levels of AGEs in serum and the colonic muscle layer, respectively. Colon transit time was measured by glass bead expul- sion test, and the contractility of circular smooth muscle strips was tested using the MPA analysis system. The protein expression level of myosin light chain kinase （MLCK） was determined by Western blot. RESULTS： Compared with the normal control group, the expression levels of AGEs in the colonic muscle layer and serum （3.00 μg/mL ± 0.34 μg/mL vs 4.31 μg/mL ± 0.73 μg/mL, P 〈 0.01） were increased, colon transit time was delayed （209.50 min ± 48.88 min vs 297.00 min ± 35.71 min, P 〈 0.01）, the contractility of circular smooth muscle strips was weakened （2.17 g ± 0.57 g vs 0.80 g ± 0.34 g, P 〈 0.01）, and the expression of MLCK in the colonic muscle layer was lower （1.46 ± 0.11 vs 1.01 ± 0.08, P 〈 0.01） in the diabetic group. There was no significant change in blood glucose levels in rats treated with AG. Com- pared with the diabetic group, DM rats treated with AG showed decreased levels of AGEs in the colon muscle layer and serum （4.31 μg/mL ± 0.73 μg/mL vs 3.35 μg/mL ± 0.58 μg/mL, P 〈 0.05）, shortened colon transit time （297.00 min ± 35.71 min vs 212.13 min ± 42.95 min, P 〈 0.01）, enhanced contractility of circular smooth muscle strips （0.80 g ± 0.34 g vs 1.49 g ± 0.44 g, P 〈 0.01）, and higher expression of MLCK in th

关 键 词：糖基化终末产物 结肠动力 肌球蛋白轻链激酶 糖尿病 大鼠 

分 类 号：R587.2[医药卫生—内分泌] R574.62[医药卫生—内科学]