CAJ | 학술논문

目的探讨匹伐他汀通过影响脂肪ClC-3氯通道介导其降脂作用以及对2型糖尿病胰岛素抵抗的治疗作用及机制.方法采用高糖高脂饮食加小剂量链脲佐菌素(STZ)诱导2型糖尿病(T2DM)大鼠模型.将大鼠随机分为模型组、匹伐他汀治疗组[3mg/(kg·d)]、吡格列酮标准治疗组[20mg/(kg·d)],并设立正常对照组,每组10只.经药物灌胃治疗5周后处死大鼠,检测空腹血糖、血脂和血清胰岛素,以计算胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数,Western Blotting检测腹腔附睾脂肪组织ClC-3蛋白表达.此外,用同样方法建立野生型小鼠及ClC-3基因敲除小鼠T2DM模型,成模5周后处死小鼠,并检测上述指标.结果与正常对照组比较,T2DM大鼠空腹血糖、血脂和HOMA-IR均明显升高,脂肪ClC-3蛋白表达水平上调(n =10,t=-2.915,P=0.017).匹伐他汀治疗5周后可使T2DM大鼠血脂、HOMA-IR明显下降,脂肪ClC-3蛋白表达明显下调(t=6.004,P＜0.01).并且T2DM大鼠的血脂、HOMA-IR与脂肪ClC-3蛋白表达水平呈明显正相关(P＜0.05).吡格列酮治疗5周后虽可使空腹血糖、血脂和HOMA-IR水平较模型组明显下降(P＜0.05),但对脂肪ClC-3蛋白表达无明显影响.与野生型T2DM小鼠比较,ClC-3基因敲除T2DM小鼠空腹血糖、血脂、HOMA-IR水平也明显下降(n=12,P＜0.05).结论匹伐他汀降低2型糖尿病大鼠的血脂水平并明显改善胰岛素抵抗,可能与其降低脂肪ClC-3氯通道蛋白表达有关.
목적 탐토필벌타정통과영향지방ClC-3록통도개도기강지작용이급대2형당뇨병이도소저항적치료작용급궤제.방법 채용고당고지음식가소제량련뇨좌균소(STZ)유도2형당뇨병(T2DM)대서모형.장대서수궤분위모형조、필벌타정치료조[3mg/(kg·d)]、필격렬동표준치료조[20mg/(kg·d)],병설립정상대조조,매조10지.경약물관위치료5주후처사대서,검측공복혈당、혈지화혈청이도소,이계산이도소저항지수(HOMA-IR)화이도소민감지수,Western Blotting검측복강부고지방조직ClC-3단백표체.차외,용동양방법건립야생형소서급ClC-3기인고제소서T2DM모형,성모5주후처사소서,병검측상술지표.결과 여정상대조조비교,T2DM대서공복혈당、혈지화HOMA-IR균명현승고,지방ClC-3단백표체수평상조(n =10,t=-2.915,P=0.017).필벌타정치료5주후가사T2DM대서혈지、HOMA-IR명현하강,지방ClC-3단백표체명현하조(t=6.004,P＜0.01).병차T2DM대서적혈지、HOMA-IR여지방ClC-3단백표체수평정명현정상관(P＜0.05).필격렬동치료5주후수가사공복혈당、혈지화HOMA-IR수평교모형조명현하강(P＜0.05),단대지방ClC-3단백표체무명현영향.여야생형T2DM소서비교,ClC-3기인고제T2DM소서공복혈당、혈지、HOMA-IR수평야명현하강(n=12,P＜0.05).결론 필벌타정강저2형당뇨병대서적혈지수평병명현개선이도소저항,가능여기강저지방ClC-3록통도단백표체유관.
Objective To explore the mechanisms of pitavastatin on antilipemic effect and insulin resistance in type 2 diabetes mellitus (T2DM) by regulating voltage gated chloride channel (ClC-3) of adipose tissue.Methods T2DM rats were randomly divided into three groups (n =10 per group):model group,pitavastatin group [3 mg/(kg · d)],and pioglitazone standard treatment group [20 mg/(kg · d)].In addition,ten normal rats were set for normal control group.The rats were given drugs or the same amount of distilled water by gastric delivery every day.After 5 weeks,all the rats were killed,blood and epididymal adipose tissue were collected.Fasting blood glucose (FBG),triglyceride (TG),free fatty acid (FFA),and insulin (FINS) in the serum of each group were determined,and then the insulin resistance index (HOMA-IR) was calculated.The expression level of ClC-3 protein level in adipose tissue was determined by Western blotting.T2DM models of wild type mice and ClC-3 gene-knockout mice were established with the same way,and the same indices were tested.Results Compared to normal control group,the levels of FBG,TG,FFA,and HOMA-IR in serum of T2DM rats were increased significantly,and the expression of adipose ClC-3 protein was upregulated significantly (n =10,t =-2.915,P =0.017).After pitavastatin treatment for 5 weeks,not only the serum levels of TG,FFA,and HOMA-IR but also the expression of ClC-3 protein were significantly decreased compared to T2DM rats (t =6.004,P ＜ 0.01).There was a significantly positive correlation between elevation levels of serum parameters (TG,FFA,and HOMA-IR) and upregulation of ClC-3 protein expression in T2DM rats.Treatment of T2DM rats with pioglitazone also decreased the levels of FBG,TG,FFA,and HOMA-IR (P ＜ 0.05),but did not affect the expression of ClC-3 protein in adipose tissue compared to the model group.Moreover,the levels of FBG,TG,FFA,HOMA-IR,and insulin sensitivity tolerance were significantly decreased in CIC-3 gene knockout-T2DM mice compared to the wild type T2DM mice (n =12,P ＜ 0.05).Conclusions Pitavastatin can decrease the blood lipid level and improve insulin resistance of T2DM rats,probably by down-regulating the expression of ClC-3 protein in adipose tissue.