中华烧伤杂志
中華燒傷雜誌
중화소상잡지
16
2011年
2期
139-144
,共6页
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
糖尿病神經病變%葡萄糖代謝障礙%糖基化終產物,高級%傷口愈閤
당뇨병신경병변%포도당대사장애%당기화종산물,고급%상구유합
Diabetic neuropathies%Glucose metabolism disorders%Glycosylation end products,advanced%Wound healing
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面愈合进程最终导致创面难愈.氨基胍和胰岛素可以减少糖尿病皮肤组织糖含量和AGE含量,改善皮肤神经病变.
目的 研究糖尿病皮膚組織糖代謝紊亂與皮膚神經病變的關繫,進一步探討神經病變與創麵難愈的機製.方法80隻SD大鼠按隨機抽籤法分為正常對照組、糖尿病對照組、氨基胍榦預組和胰島素榦預組,每組20隻.後3組通過腹腔註射鏈脲佐菌素(STZ)誘導糖尿病模型.誘導後1週,氨基胍榦預組胃管飼人氨基胍100 mg·kg-1·d-1,胰島素榦預組皮下註射胰島素將血糖控製在正常範圍.分彆于註射STZ後2、4、8週,觀察大鼠後肢足掌部機械痛和熱痛閾值變化併穫取大鼠足掌部皮膚標本.檢測皮膚組織中糖含量、晚期糖基化終末產物(AGE)含量、神經纖維變化及神經肽P物質和降鈣素基因相關肽(CGRP)含量.對數據進行t檢驗.結果糖尿病對照組大鼠機械痛、熱痛閾值在註射STZ後2週時分彆為(6.3±1.5)g、(6.0±0.9)s,明顯低于正常對照組的(13.0±3.2)g、(10.3±1.2)s,t值分彆為2.71、3.42,P值均小于0.05;皮膚組織糖和AGE含量均明顯增加,8週時各為(2.85±0.33)mg/g、(31.7±3.2)U/mg,明顯高于正常對照組[(0.82±0.22)mg/g、(22.2±1.9)U/mg,t值分彆為1.65、6.47,P值均小于0.01];有髓神經纖維髓鞘水腫變性、軸突被擠壓,無髓神經纖維水腫空泡化、微絲微管排列紊亂;P物質含量2週時降至低穀[(16.8±3.4)pg/g],明顯低于正常對照組[(28.5±5.0)pg/g,t=2.42,P＜0.01];CGRP含量變化不明顯.與糖尿病對照組比較,氨基胍榦預組大鼠皮膚組織糖含量無明顯改變,8週時AGE含量明顯減少[(27.2±1.4)U/mg,t=3.38,P＜0.05];胰島素榦預組糖含量和AGE含量均明顯減少,8週時分彆為(1.42±0.38)mg/g、(23.6±1.3)U/mg,t值分彆為1.74、8.17,P＜0.05或P＜0.01.2箇榦預組P物質下降幅度減輕,低穀滯後;CGRP含量無明顯變化.結論高糖和AGE蓄積是導緻糖尿病皮膚神經病變的重要原因,使糖尿病皮膚具有不同于正常皮膚的創傷起點,可在傷後持續影響創麵愈閤進程最終導緻創麵難愈.氨基胍和胰島素可以減少糖尿病皮膚組織糖含量和AGE含量,改善皮膚神經病變.
목적 연구당뇨병피부조직당대사문란여피부신경병변적관계,진일보탐토신경병변여창면난유적궤제.방법80지SD대서안수궤추첨법분위정상대조조、당뇨병대조조、안기고간예조화이도소간예조,매조20지.후3조통과복강주사련뇨좌균소(STZ)유도당뇨병모형.유도후1주,안기고간예조위관사인안기고100 mg·kg-1·d-1,이도소간예조피하주사이도소장혈당공제재정상범위.분별우주사STZ후2、4、8주,관찰대서후지족장부궤계통화열통역치변화병획취대서족장부피부표본.검측피부조직중당함량、만기당기화종말산물(AGE)함량、신경섬유변화급신경태P물질화강개소기인상관태(CGRP)함량.대수거진행t검험.결과당뇨병대조조대서궤계통、열통역치재주사STZ후2주시분별위(6.3±1.5)g、(6.0±0.9)s,명현저우정상대조조적(13.0±3.2)g、(10.3±1.2)s,t치분별위2.71、3.42,P치균소우0.05;피부조직당화AGE함량균명현증가,8주시각위(2.85±0.33)mg/g、(31.7±3.2)U/mg,명현고우정상대조조[(0.82±0.22)mg/g、(22.2±1.9)U/mg,t치분별위1.65、6.47,P치균소우0.01];유수신경섬유수초수종변성、축돌피제압,무수신경섬유수종공포화、미사미관배렬문란;P물질함량2주시강지저곡[(16.8±3.4)pg/g],명현저우정상대조조[(28.5±5.0)pg/g,t=2.42,P＜0.01];CGRP함량변화불명현.여당뇨병대조조비교,안기고간예조대서피부조직당함량무명현개변,8주시AGE함량명현감소[(27.2±1.4)U/mg,t=3.38,P＜0.05];이도소간예조당함량화AGE함량균명현감소,8주시분별위(1.42±0.38)mg/g、(23.6±1.3)U/mg,t치분별위1.74、8.17,P＜0.05혹P＜0.01.2개간예조P물질하강폭도감경,저곡체후;CGRP함량무명현변화.결론고당화AGE축적시도치당뇨병피부신경병변적중요원인,사당뇨병피부구유불동우정상피부적창상기점,가재상후지속영향창면유합진정최종도치창면난유.안기고화이도소가이감소당뇨병피부조직당함량화AGE함량,개선피부신경병변.
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 ＜ 0.01]. There was no obvious difference in content of CGRP between NC and D groups, and also in content of glucose in skin between D and AⅠ groups. Compared with those in D group, content of AGE in AⅠ group at PIW 8 was decreased markedly [(27.2 ± 1.4) U/mg of hydroxyproline, t = 3.38, P ＜0.05]; contents of glucose and AGE in Ⅱ group at PIW 8 were significantly decreased [( 1.42 ± 0.38 ) mg/g,(23.6 ± 1.3 ) U/mg of hydroxyproline, with t value respectively 1.74, 8.17, P ＜ 0.05 or P ＜ 0. 01].Compared with that in D group, contents of SP in AⅠ and Ⅱ groups were increased, with a delay in time of trough value. Content of CGRP showed no obvious difference among D, AⅠ, and Ⅱ groups. Conclusions High glucose and accumulation of AGE are key mediators of cutaneous neuropathy and impaired wound healing in diabetes mellitus, which confirms that diabetic wound takes an atypical footing during wound repairing. Aminoguanidine and insulin can reduce contents of glucose and AGE in diabetic skin tissue, and ameliorate diabetic cutaneous neuropathy.
