中华生物医学工程杂志
中華生物醫學工程雜誌
중화생물의학공정잡지
CHINESE JOURNAL OF BIOMEDICAL ENGINEERING
2014年
1期
12-16
,共5页
徐谦%曹柳%刘琼%刘宽芝
徐謙%曹柳%劉瓊%劉寬芝
서겸%조류%류경%류관지
糖尿病,2型%Toll样受体4%肌,骨骼%辛伐他汀%大鼠,Sprague-Dawley
糖尿病,2型%Toll樣受體4%肌,骨骼%辛伐他汀%大鼠,Sprague-Dawley
당뇨병,2형%Toll양수체4%기,골격%신벌타정%대서,Sprague-Dawley
Diabetes mellitus,type 2%Toll-like receptors 4%Muscle,skeletal%Simvastatin%Rats,Sprague-Dawley
目的 探讨2型糖尿病大鼠骨骼肌组织Toll样受体4(TLR4)的表达及辛伐他汀的干预作用.方法 以高脂高糖饲料联合小剂量链脲佐菌素喂养SD大鼠制备2型糖尿病大鼠模型(26只),随机分为糖尿病组(n=13)和辛伐他汀干预组(n=13),正常SD大鼠(n=10)作为对照组.辛伐他汀干预组给予辛伐他汀20 mg·kg-1·d-1灌胃,糖尿病组和对照组均给予等体积生理盐水灌胃.8周后检测各组大鼠血糖、血脂、肌酸激酶水平;光镜观察骨骼肌组织学改变;免疫组织化学检测骨骼肌TLR4蛋白的表达;RT-PCR法检测骨骼肌TLR4 mRNA的表达.结果 糖尿病组和辛伐他汀干预组空腹血糖较对照组明显升高[(12.04±2.04) mmol/L、(11.23±2.61) mmol/L比(5.92± 1.28) mmol/L,均P＜0.05],糖尿病组和辛伐他汀干预组两组之间空腹血糖水平差异无统计学意义.3组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平糖尿病组＞辛伐他汀干预组＞对照组(均P＜0.05);高密度脂蛋白胆固醇(HDL-C)水平对照组＞辛伐他汀干预组＞糖尿病组(均P＜0.05).3组肌酸激酶之间差异无统计学意义.对照组大鼠骨骼肌肌膜完整、清晰,肌纤维排列紧密;糖尿病组大鼠部分肌纤维萎缩、变性、水肿,肌纤维断裂,肌丝走行紊乱,并可见炎性细胞浸润;辛伐他汀干预组大鼠病理改变较糖尿病组减轻.糖尿病组TLR4蛋白表达水平是对照组的1.54倍[0.318±0.037比0.206±0.024,P＜0.05],辛伐他汀干预组TLR4蛋白表达水平0.256±0.035,是糖尿病组的80.50％ (P＜ 0.05).糖尿病组TLR4 mRNA水平是对照组的1.62倍[0.625±0.074比0.385±0.088,P＜0.05],辛伐他汀干预组TLR4 mRNA水平0.501±0.105,是糖尿病组的80.16％(P＜ 0.05).结论 糖尿病性骨骼肌病变与TLR4高表达相关,辛伐他汀可能通过降低骨骼肌TLR4的表达从而减轻骨骼肌病变.
目的 探討2型糖尿病大鼠骨骼肌組織Toll樣受體4(TLR4)的錶達及辛伐他汀的榦預作用.方法 以高脂高糖飼料聯閤小劑量鏈脲佐菌素餵養SD大鼠製備2型糖尿病大鼠模型(26隻),隨機分為糖尿病組(n=13)和辛伐他汀榦預組(n=13),正常SD大鼠(n=10)作為對照組.辛伐他汀榦預組給予辛伐他汀20 mg·kg-1·d-1灌胃,糖尿病組和對照組均給予等體積生理鹽水灌胃.8週後檢測各組大鼠血糖、血脂、肌痠激酶水平;光鏡觀察骨骼肌組織學改變;免疫組織化學檢測骨骼肌TLR4蛋白的錶達;RT-PCR法檢測骨骼肌TLR4 mRNA的錶達.結果 糖尿病組和辛伐他汀榦預組空腹血糖較對照組明顯升高[(12.04±2.04) mmol/L、(11.23±2.61) mmol/L比(5.92± 1.28) mmol/L,均P＜0.05],糖尿病組和辛伐他汀榦預組兩組之間空腹血糖水平差異無統計學意義.3組總膽固醇(TC)、三酰甘油(TG)、低密度脂蛋白膽固醇(LDL-C)水平糖尿病組＞辛伐他汀榦預組＞對照組(均P＜0.05);高密度脂蛋白膽固醇(HDL-C)水平對照組＞辛伐他汀榦預組＞糖尿病組(均P＜0.05).3組肌痠激酶之間差異無統計學意義.對照組大鼠骨骼肌肌膜完整、清晰,肌纖維排列緊密;糖尿病組大鼠部分肌纖維萎縮、變性、水腫,肌纖維斷裂,肌絲走行紊亂,併可見炎性細胞浸潤;辛伐他汀榦預組大鼠病理改變較糖尿病組減輕.糖尿病組TLR4蛋白錶達水平是對照組的1.54倍[0.318±0.037比0.206±0.024,P＜0.05],辛伐他汀榦預組TLR4蛋白錶達水平0.256±0.035,是糖尿病組的80.50％ (P＜ 0.05).糖尿病組TLR4 mRNA水平是對照組的1.62倍[0.625±0.074比0.385±0.088,P＜0.05],辛伐他汀榦預組TLR4 mRNA水平0.501±0.105,是糖尿病組的80.16％(P＜ 0.05).結論 糖尿病性骨骼肌病變與TLR4高錶達相關,辛伐他汀可能通過降低骨骼肌TLR4的錶達從而減輕骨骼肌病變.
목적 탐토2형당뇨병대서골격기조직Toll양수체4(TLR4)적표체급신벌타정적간예작용.방법 이고지고당사료연합소제량련뇨좌균소위양SD대서제비2형당뇨병대서모형(26지),수궤분위당뇨병조(n=13)화신벌타정간예조(n=13),정상SD대서(n=10)작위대조조.신벌타정간예조급여신벌타정20 mg·kg-1·d-1관위,당뇨병조화대조조균급여등체적생리염수관위.8주후검측각조대서혈당、혈지、기산격매수평;광경관찰골격기조직학개변;면역조직화학검측골격기TLR4단백적표체;RT-PCR법검측골격기TLR4 mRNA적표체.결과 당뇨병조화신벌타정간예조공복혈당교대조조명현승고[(12.04±2.04) mmol/L、(11.23±2.61) mmol/L비(5.92± 1.28) mmol/L,균P＜0.05],당뇨병조화신벌타정간예조량조지간공복혈당수평차이무통계학의의.3조총담고순(TC)、삼선감유(TG)、저밀도지단백담고순(LDL-C)수평당뇨병조＞신벌타정간예조＞대조조(균P＜0.05);고밀도지단백담고순(HDL-C)수평대조조＞신벌타정간예조＞당뇨병조(균P＜0.05).3조기산격매지간차이무통계학의의.대조조대서골격기기막완정、청석,기섬유배렬긴밀;당뇨병조대서부분기섬유위축、변성、수종,기섬유단렬,기사주행문란,병가견염성세포침윤;신벌타정간예조대서병리개변교당뇨병조감경.당뇨병조TLR4단백표체수평시대조조적1.54배[0.318±0.037비0.206±0.024,P＜0.05],신벌타정간예조TLR4단백표체수평0.256±0.035,시당뇨병조적80.50％ (P＜ 0.05).당뇨병조TLR4 mRNA수평시대조조적1.62배[0.625±0.074비0.385±0.088,P＜0.05],신벌타정간예조TLR4 mRNA수평0.501±0.105,시당뇨병조적80.16％(P＜ 0.05).결론 당뇨병성골격기병변여TLR4고표체상관,신벌타정가능통과강저골격기TLR4적표체종이감경골격기병변.
Objective To investigate the expression of Toll like receptor 4 (TLR4) in skeletal muscle of type2 diabetic rats and the intervention effect of simvastatin.Methods The type 2 diabetic rat model was established in 26 SD rats by feeding high-fat,high-sucrose diet and injecting low dose of streptozotocin (STZ).These rats were randomly divided into diabetic group (13 rats) and simvastatin group (13 rats),with 10 normal SD rats as control group.The rats in simvastatin group received simvastatin at a dosage of 20 mg· kg-1 · d-1 by gastric gavage while the ones in normal control group (10 rats) and diabetic group received equal volume of normal saline by gastric gavage.After 8 weeks,fasting blood glucose(FBG),blood lipids and creatine kinase (CK)were measured in all groups,and histological change in skeletal muscle of all rats were observed.The protein and mRNA expression of TLR4 in skeletal muscle was examined by immunohistochemistry staining and RT-PCR respectively.Results FBG of diabetes group and simvastatin group were significantly higher than that of control group [(12.04 ± 2.04) mmol/L,(11.23 ± 2.61) mmol/L vs (5.92± 1.28)mmol/L,all P ＜ 0.05],and there were no significant difference of FBG between diabetes group and simvastatin group.The levels of TG,TC and LDL-C in three groups were diabetes group＞simvastatin group＞control group (all P ＜ 0.05).Levels of HDL-C in three groups were control group＞simvastatin group＞diabetes group (all P ＜ 0.05).There were no significant differences of creatine kinase among three groups.Skeletal muscle of normal control group rats was complete and orderly,muscle fibers arranged in cloes while the morphology of skeletal muscle of diabetic rats was atrophic,fractured and edamed,muscle fiber ruptured and filaments traveling disordered with observed infiltration of inflammatory cells,and such changes were extenuated in simvastatin group.The expression level of TLR4 protein in diabetes group was 1.54 times of control group(0.318±0.037 vs 0.206±0.024,P ＜ 0.05) and level of TLR4 protein in simvastatin group was 80.50％ of diabetes group (0.256±0.035 vs 0.318±0.037,P＜ 0.05).The level of TLR4 mRNA in diabetes group was 1.62 times of control group (0.625±0.074 vs 0.385±0.088,P ＜ 0.05) and level of TLR4 mRNA in simvastatin group was 80.16％ of diabetes group (0.501 ±0.105 vs 0.625 ±0.074,P＜ 0.05).Conclusions Diabetic skeletal muscle lesions is associated with high expression of TLR4.Skeletal muscle lesions may be mitigated by simvastatin through down-regulating TLR4 expression in skeletal muscle.
