国际内分泌代谢杂志
國際內分泌代謝雜誌
국제내분비대사잡지
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2014年
6期
365-370
,共6页
赵紫琴%雒瑢%田凤石%郑喜兰
趙紫琴%雒瑢%田鳳石%鄭喜蘭
조자금%락용%전봉석%정희란
替米沙坦%2型糖尿病%过氧化物酶体增殖物活化受体γ%脂肪组织
替米沙坦%2型糖尿病%過氧化物酶體增殖物活化受體γ%脂肪組織
체미사탄%2형당뇨병%과양화물매체증식물활화수체γ%지방조직
Telmisartan%Type 2 diabetes mellitus%Peroxisome proliferator-activated receptor γ%Adipose tissue
目的 探讨替米沙坦对高脂饲养的OLETF大鼠皮下、内脏脂肪组织中过氧化物酶体增殖物活化受体(PPAR)γ1、PPARγ2基因表达的调控作用及其部位差异性.方法 4周龄雄性OLETF大鼠30只,性别、周龄匹配的正常非糖尿病LETO大鼠12只作为对照,OLETF大鼠从8周龄开始给予高脂喂养,22周龄时,口服葡萄糖耐量试验(OGTT)未发生临床糖尿病或糖耐量减低.之后将这些糖尿病前期OLETF大鼠按照随机数字表法分为替米沙坦干预组(O-T组,5 mg· kg-1 ·d-1,n=10)、吡格列酮干预组(O-P组,10 mg·kg-1·d-1,n=8)和无干预对照组(O-C组,生理盐水,n=10),LETO大鼠为对照组(n=12).48周龄时,复查OGTT,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR).ELISA法测定血清PPARγ的水平,实时PCR检测皮下和睾周脂肪组织中PPARγ1和PPARγ2的基因表达,并测定各组脂肪细胞的面积.结果 与O-C组相比,O-T组皮下脂肪中PPARγ2的表达明显升高(P＜0.01),且O-T组与O-P组之间差异无统计学意义.O-T组内脏脂肪组织中PPARγ1和PPARγ2的表达也明显上调(P＜0.01),HOMA-IR与内脏脂肪组织中PPARγ2的mRNA表达水平呈负相关(ρ=-0.369,P=0.021).与O-C组相比,O-T组脂肪细胞面积减少56％(P＜0.01).结论替米沙坦可部分激活PPARγ,上调皮下及内脏脂肪组织中PPARγ1和PPARγ2的表达,减小脂肪细胞面积,增加胰岛素敏感性.
目的 探討替米沙坦對高脂飼養的OLETF大鼠皮下、內髒脂肪組織中過氧化物酶體增殖物活化受體(PPAR)γ1、PPARγ2基因錶達的調控作用及其部位差異性.方法 4週齡雄性OLETF大鼠30隻,性彆、週齡匹配的正常非糖尿病LETO大鼠12隻作為對照,OLETF大鼠從8週齡開始給予高脂餵養,22週齡時,口服葡萄糖耐量試驗(OGTT)未髮生臨床糖尿病或糖耐量減低.之後將這些糖尿病前期OLETF大鼠按照隨機數字錶法分為替米沙坦榦預組(O-T組,5 mg· kg-1 ·d-1,n=10)、吡格列酮榦預組(O-P組,10 mg·kg-1·d-1,n=8)和無榦預對照組(O-C組,生理鹽水,n=10),LETO大鼠為對照組(n=12).48週齡時,複查OGTT,計算穩態模型評估-胰島素牴抗指數(HOMA-IR).ELISA法測定血清PPARγ的水平,實時PCR檢測皮下和睪週脂肪組織中PPARγ1和PPARγ2的基因錶達,併測定各組脂肪細胞的麵積.結果 與O-C組相比,O-T組皮下脂肪中PPARγ2的錶達明顯升高(P＜0.01),且O-T組與O-P組之間差異無統計學意義.O-T組內髒脂肪組織中PPARγ1和PPARγ2的錶達也明顯上調(P＜0.01),HOMA-IR與內髒脂肪組織中PPARγ2的mRNA錶達水平呈負相關(ρ=-0.369,P=0.021).與O-C組相比,O-T組脂肪細胞麵積減少56％(P＜0.01).結論替米沙坦可部分激活PPARγ,上調皮下及內髒脂肪組織中PPARγ1和PPARγ2的錶達,減小脂肪細胞麵積,增加胰島素敏感性.
목적 탐토체미사탄대고지사양적OLETF대서피하、내장지방조직중과양화물매체증식물활화수체(PPAR)γ1、PPARγ2기인표체적조공작용급기부위차이성.방법 4주령웅성OLETF대서30지,성별、주령필배적정상비당뇨병LETO대서12지작위대조,OLETF대서종8주령개시급여고지위양,22주령시,구복포도당내량시험(OGTT)미발생림상당뇨병혹당내량감저.지후장저사당뇨병전기OLETF대서안조수궤수자표법분위체미사탄간예조(O-T조,5 mg· kg-1 ·d-1,n=10)、필격렬동간예조(O-P조,10 mg·kg-1·d-1,n=8)화무간예대조조(O-C조,생리염수,n=10),LETO대서위대조조(n=12).48주령시,복사OGTT,계산은태모형평고-이도소저항지수(HOMA-IR).ELISA법측정혈청PPARγ적수평,실시PCR검측피하화고주지방조직중PPARγ1화PPARγ2적기인표체,병측정각조지방세포적면적.결과 여O-C조상비,O-T조피하지방중PPARγ2적표체명현승고(P＜0.01),차O-T조여O-P조지간차이무통계학의의.O-T조내장지방조직중PPARγ1화PPARγ2적표체야명현상조(P＜0.01),HOMA-IR여내장지방조직중PPARγ2적mRNA표체수평정부상관(ρ=-0.369,P=0.021).여O-C조상비,O-T조지방세포면적감소56％(P＜0.01).결론체미사탄가부분격활PPARγ,상조피하급내장지방조직중PPARγ1화PPARγ2적표체,감소지방세포면적,증가이도소민감성.
Objective To explore the regulation of telmisartan on expression of peroxisome proliferator-activated receptor(PPAR) 1 and PPARγ2 in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in high-fat diet fed OLETF rats and their tissue difference.Methods Thirty four-week-old male OLETF rats were selected and 12 gender-and age-matched Long-Evans Tokushima Otsuka(LETO) rats were used as normal control.From 8 weeks of age,the OLETF rats were fed with high-fat diet.At 22 weeks of age,there was no case of impaired glucose tolerance or type 2 diabetes mellitus in OLETF rats tested by oral glucose tolerance test (OGTT).Then,these pre-diabetic OLETF rats were divided into telmisartan group (O-T group,5 mg· kg-1 · d-1,n =10),pioglitazone group (O-P group,10 mg · kg-1 · d-1,n=8),and untreated control group (O-T group,n =10) according to the radom number table.LETO (n =12) rats were used as control group.OGTT was carried out at 48 weeks of age,and homeostasis model assessment of insulin resistance(HOMA-IR)was evaluated.Serum PPARγwas measured using ELISA.The mRNA levels of PPARγ1 and PPARγ2 in different fatty tissues were determined by real-time PCR.The adipocyte sizes were also assessed.Results Compared with O-C group,the PPARγ2 level in SAT was significantly up-regulated in O-T group(P ＜0.01),while no difference was observed between O-T and O-P group.In addition,both PPARγ1 and PPARγ2 mRNA levels in VAT were up-regulated in O-T group (P ＜0.01).There was a negative correlation bctween HOMA-IR and PPARγ2 mRNA expression in VAT (ρ =-0.369,P =0.021).Compared with O-C group,the adipose cell size was decreased by 56％ in O-T group.Conclusion Telnisartan can at least partially up-regulate the expression of PPARγ,1 and PPARγ2 in SAT and VAT,decrease the adipose cell size,and improve insulin sensitivity by activating PPARγ.
