罗格列酮对糖尿病大鼠骨骼肌损害防护作用的机制研究

目的探讨罗格列酮对糖尿病大鼠骨骼肌损害防护作用的机制。方法用链脲佐菌素(STZ)将39只10周龄雄性Wistar大鼠诱导成糖尿病大鼠模型,分为胰岛素治疗组、罗格列酮治疗组、未治疗组(每组13只),并以13只正常大鼠作对照。于第16周末抽取各组大鼠心脏血测定TNF-α、IL-6、C-反应蛋白、SOD、P物质水平,并处死取股二头肌进行病理学观察;用免疫组织化学染色观察骨骼肌中晚期糖基化终末产物(AGEs)与过氧化物酶体增殖物激活受体(PPAR-γ)含量的变化。结果未治疗组血清IL-6、TNF-α、C-反应蛋白水平均明显高于正常组(P<0.05),胰岛素组和罗格列酮组则与正常对照组比较无差异;未治疗组血清SOD、SP水平与正常组相比明显降低(P<0.01),胰岛素组和罗格列酮组的SOD和P物质二者显著高于糖尿病组(P<0.01,P<0.05)。组织学观察:糖尿病组骨骼肌普遍萎缩,肌纤维横截面积明显缩小;部分肌纤维变性,间质水肿,炎细胞浸润;胰岛素组和罗格列酮组骨骼肌有部分轻度萎缩,间质轻度水肿,少量淋巴细胞浸润。免疫组织化学显示:AGEs蛋白、PPAR-γ蛋白均呈棕黄色颗粒状,弥漫或斑片状沉积于骨骼肌细胞胞浆中;在糖尿病组AGEs最高,PPAR-γ最低。结论糖尿病大鼠受损的骨骼肌中有AGEs蓄积和血清炎症因子增高,罗格列酮对糖尿病大鼠骨骼肌损害具有防护作用。

Rosiglitazone on Skeletal Muscle Damage in Diabetic rats the Mechanism of Protective Effect

Objective To stuty the protective effect ofrosiglitazone on skeletal muscle damage in diabetic rats. Methods The rats were divided into normal control group （C group, n =13）, diabetic control group （DC group, n=13）,diabetes and insulin treatment group （D I group, n =13）, diabetes and rosiglitazone treatment group （DR group, n =13）. The diabetic rat models were established with high fat diet for 2 weeks followed by intraperitoneal injection of 35 mg/kg streptozotocin injection, the ratswere idenfied as diabetic when their fasting blood glucose （FBG） over 7.0remoVE The living ratswere given corresponding treatment, subcutaneous injection of I to 2 U/d insulin, intragastric injection of 5mg/（kgod） rosiglitazone,or sterile water. Heart blood samp les of rats from each group were collected to measure TNF-α, IL-6, C-RP, SOD and P material levels in the 16th weekend. Also the Biceps femoris was taken for pathological observation.Use of chemical stain to see the Biceps femoris was poorly organized in the AGEs and PPAR-gamma content changes. Results The levels of IL-6, TNF-α and C-RP of all the diabetic model groups were significantly higher than those of the normal group （P〈0.05）,No difference was observed in DI and DR groups compared with the normal control group; the SOD and SP level in diabetic group was significantly lower than that in the normal group （P〈0.01）,the SOD and SP levels were significantly increased in insulin and rosiglitazone groups compared with Diabetes Group （P〈0.01,P〈0.05）. Organization to observe ：Skeletal muscle of diabetic group generally atrophy, muscle fiber cross-sectional area was significantly reduced; part of the muscle fiber degeneration, interstitial edema, inflammatory cell infiltration; insulin group and part of the rosiglitazone group skeletal muscle atrophy, mild interstitial edema, a small amount of lymphoidcell infiltration. Immunohistochemistry showed that： of AGEs protein,PPAR-~, protein showed brown yellow granular, diffuse or patchy deposition in the skeletal muscle cell cytoplasm; AGEs highest in the diabetic group, the lowest of PPAR-gamma. Conclusion Diabetic rats impaired skeletal muscle, increased AGEs accumulation and serum inflammatory factors, rosiglitazone and insulin in diabetic rat skeletal muscle damage as a protective effect.