糖尿病大鼠皮肤组织糖代谢紊乱与皮肤神经病变相关性研究  

Relationship between cutaneous glycometabolic disorders and cutaneous neuropathy in diabetic rats

作　　者：陈宾[1] 牛轶雯[1] 谢挺[2] 缪明远[1] 田鸣[1] 嵇晓芸[1] 青春[1] 陆树良[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院上海市烧伤研究所,200025 [2]上海交通大学医学院附属第九人民医院创面修复科

出　　处：《中华烧伤杂志》2011年第2期139-144,共6页Chinese Journal of Burns

基　　金：国家重点基础研究发展计划（2005CB522603）;国家自然科学基金（81071568、30471784、30600645、30700871）

摘　　要：目的 研究糖尿病皮肤组织糖代谢紊乱与皮肤神经病变的关系,进一步探讨神经病变与创面难愈的机制.方法80只SD大鼠按随机抽签法分为正常对照组、糖尿病对照组、氨基胍干预组和胰岛素干预组,每组20只.后3组通过腹腔注射链脲佐菌素（STZ）诱导糖尿病模型.诱导后1周,氨基胍干预组胃管饲人氨基胍100 mg·kg-1·d-1,胰岛素干预组皮下注射胰岛素将血糖控制在正常范围.分别于注射STZ后2、4、8周,观察大鼠后肢足掌部机械痛和热痛阈值变化并获取大鼠足掌部皮肤标本.检测皮肤组织中糖含量、晚期糖基化终末产物（AGE）含量、神经纤维变化及神经肽P物质和降钙素基因相关肽（CGRP）含量.对数据进行t检验.结果糖尿病对照组大鼠机械痛、热痛阈值在注射STZ后2周时分别为（6.3±1.5）g、（6.0±0.9）s,明显低于正常对照组的（13.0±3.2）g、（10.3±1.2）s,t值分别为2.71、3.42,P值均小于0.05;皮肤组织糖和AGE含量均明显增加,8周时各为（2.85±0.33）mg/g、（31.7±3.2）U/mg,明显高于正常对照组[（0.82±0.22）mg/g、（22.2±1.9）U/mg,t值分别为1.65、6.47,P值均小于0.01];有髓神经纤维髓鞘水肿变性、轴突被挤压,无髓神经纤维水肿空泡化、微丝微管排列紊乱;P物质含量2周时降至低谷[（16.8±3.4）pg/g],明显低于正常对照组[（28.5±5.0）pg/g,t=2.42,P＜0.01];CGRP含量变化不明显.与糖尿病对照组比较,氨基胍干预组大鼠皮肤组织糖含量无明显改变,8周时AGE含量明显减少[（27.2±1.4）U/mg,t=3.38,P＜0.05];胰岛素干预组糖含量和AGE含量均明显减少,8周时分别为（1.42±0.38）mg/g、（23.6±1.3）U/mg,t值分别为1.74、8.17,P＜0.05或P＜0.01.2个干预组P物质下降幅度减轻,低谷滞后;CGRP含量无明显变化.结论高糖和AGE蓄积是导致糖尿病皮肤神经病变的重要原因,使糖尿病皮肤具有不同于正常皮肤的创伤起点,可在伤后持续影响创�Objective To analyze the relationship between cutaneous glycometabolic disorders and cutaneous neuropathy in diabetic rats, and to look for the mechanism of neuropathy and impaired wound healing. Methods Eighty male SD rats were randomly divided into the normal control group （NC, n =20 ）, diabetic group （D, n = 20 ）, aminoguanidine-interfered group （AⅠ, n = 20 ）, and insulin-interfered group （ Ⅱ, n = 20） by drawing lots. Diabetes was reproduced in rats of D, AⅠ, and Ⅱ groups with intraperoguanidine, while rats in Ⅱ group were subcutaneously injected with insulin for satisfactory control of blood glucose. Changes in mechanical and heat pain thresholds of pad of hind limb were measured at post injection week （ PIW ） 2, 4, 8. Skin specimens were collected during PIW 2-8 from pads for determination of contents of glucose, advanced glycation end product （ AGE）, substance P （ SP）, calcitonin gene-related peptide （ CGRP）, and observation of distribution and ultrastructure of skin nerve fibers. Data were processed with t test. Results The mechanical and heat pain thresholds in D group at PIW 2 [（6.3 ± 1.5） g, （6.0 ±0.9） s, respectively] were obviously lower than those in NC group [（13.0 ±3.2） g, （10.3 ± 1.2） s,with t value respectively 2.71, 3.42, P values all below 0.05]. Contents of glucose and AGE in skin tissue in D group were significantly increased when compared with those in NC group, especially at PIW 8 [（2.85 ±0.33） mg/g, （31.7±3.2） U/mg of hydroxyproline vs. （0.82 ±0.22） mg/g, （22.2 ±1.9） U/mg of hydroxyproline, with t value respectively 1.65, 6.47, P values all below 0.01]. The myelinated nerve fibers were edematous and degenerated, with axons compressed, while the unmyelinated nerve fibers were vacuolated, with microfilament and microtubule disorderly arranged. Content of SP in skin tissue in D group was lower as compared with that in NC group, especially at PIW 2 [（16.8 ±3.4） pg/g vs. （28.5 ±5.0） pg/g,t = 2.42, P 〈

关 键 词：糖尿病神经病变 葡萄糖代谢障碍 糖基化终产物 高级 伤口愈合 

分 类 号：R587.1[医药卫生—内分泌]