中华糖尿病杂志
中華糖尿病雜誌
중화당뇨병잡지
CHINES JOURNAL OF DLABETES MELLITUS
2014年
8期
584-588
,共5页
沈山梅%金玺%房其军%毕艳%孟然%李丽蓉%石欢%韩小娟%朱大龙
瀋山梅%金璽%房其軍%畢豔%孟然%李麗蓉%石歡%韓小娟%硃大龍
침산매%금새%방기군%필염%맹연%리려용%석환%한소연%주대룡
胰岛素抵抗%氧化应激%胰岛素信号通路%津力达颗粒
胰島素牴抗%氧化應激%胰島素信號通路%津力達顆粒
이도소저항%양화응격%이도소신호통로%진력체과립
Insulin resistance%Oxidative stress%Insulin signal pathway%Jin Lida Granule
目的 观察中药津力达颗粒对高脂饮食诱导的胰岛素抵抗(IR)模型大鼠肝脏氧化应激及胰岛素信号通路的影响.方法 将36只6～8周龄雄性SD大鼠予以高脂饲料喂养12周诱导IR模型,26只成模大鼠随机数字法分为高脂组(n=8)、津力达组(n=9)、二甲双胍组(n=9),予以高脂饲料喂养,同时以健康SD大鼠设立普食组(n=9).药物干预10周后行腹腔注射葡萄糖耐量试验(IPGTT)测取0、60、120 min血糖及胰岛素水平,计算稳态模型IR指数(HOMA-IR)评价肝脏IR,胰岛素敏感指数(ISI)评价全身胰岛素敏感性,同时测定各组大鼠肝脏组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)及过氧化氢酶(CAT)等氧化指标表达.Western blotting法测定肝脏组织中c-Jun氨基末端激酶(JNK)、蛋白激酶B(PKB/Akt)及胰岛素受体底物1(IRS-1)的活性变化.采用单因素方差分析进行多组间均数比较.结果 药物干预10周后,IPGTT实验结果显示,与高脂组相比,普食组、津力达组、二甲双胍组空腹及餐后血糖及血清胰岛素水平出现不同程度下降,其中在60、120 min血糖及0、120 min胰岛素水平上均存在统计学差异(t=1.76～ 5.03,均P＜0.05),HOMA-IR出现下降,ISI明显上升(t=-187.63 ～5 635.06,均P＜0.05);与高脂组相比,二甲双胍组、津力达组SOD活性分别升高了64.9％、64.4％(t=-3 831.41、-2 879.73,均P＜0.05);MDA降低了36.3％及28.1％(t=183.52、105.77,均P＜0.05);CAT和GSH分别上升了101.0％、41.5％ (t=21.47、-512.31,均P＜0.05)及111.0％、39.8％ (t=19.68、357.20,均P＜0.05);p-JNK/JNK分别下降了26.3％及15.0％(t=0.77、0.61,均P＜0.01);p-IRS-1/IRS-1分别下降了23.5％及29.4％(t=0.61、0.46,均P＜0.01),p-Akt/Akt则上升了43.7％及42.3％(t=-0.50、-0.28,均P＜0.01).但津力达组与二甲双胍组之间差异均无统计学意义.结论 津力达颗粒可显著提高IR大鼠的胰岛素敏感性,其机制可能是津力达颗粒增强了IR大鼠肝脏的抗氧化能力,抑制肝脏组织中JNK及IRS-1的磷酸化,增加了Akt的活性,从而改善胰岛素信号的转导.
目的 觀察中藥津力達顆粒對高脂飲食誘導的胰島素牴抗(IR)模型大鼠肝髒氧化應激及胰島素信號通路的影響.方法 將36隻6～8週齡雄性SD大鼠予以高脂飼料餵養12週誘導IR模型,26隻成模大鼠隨機數字法分為高脂組(n=8)、津力達組(n=9)、二甲雙胍組(n=9),予以高脂飼料餵養,同時以健康SD大鼠設立普食組(n=9).藥物榦預10週後行腹腔註射葡萄糖耐量試驗(IPGTT)測取0、60、120 min血糖及胰島素水平,計算穩態模型IR指數(HOMA-IR)評價肝髒IR,胰島素敏感指數(ISI)評價全身胰島素敏感性,同時測定各組大鼠肝髒組織中超氧化物歧化酶(SOD)、丙二醛(MDA)、還原型穀胱甘肽(GSH)及過氧化氫酶(CAT)等氧化指標錶達.Western blotting法測定肝髒組織中c-Jun氨基末耑激酶(JNK)、蛋白激酶B(PKB/Akt)及胰島素受體底物1(IRS-1)的活性變化.採用單因素方差分析進行多組間均數比較.結果 藥物榦預10週後,IPGTT實驗結果顯示,與高脂組相比,普食組、津力達組、二甲雙胍組空腹及餐後血糖及血清胰島素水平齣現不同程度下降,其中在60、120 min血糖及0、120 min胰島素水平上均存在統計學差異(t=1.76～ 5.03,均P＜0.05),HOMA-IR齣現下降,ISI明顯上升(t=-187.63 ～5 635.06,均P＜0.05);與高脂組相比,二甲雙胍組、津力達組SOD活性分彆升高瞭64.9％、64.4％(t=-3 831.41、-2 879.73,均P＜0.05);MDA降低瞭36.3％及28.1％(t=183.52、105.77,均P＜0.05);CAT和GSH分彆上升瞭101.0％、41.5％ (t=21.47、-512.31,均P＜0.05)及111.0％、39.8％ (t=19.68、357.20,均P＜0.05);p-JNK/JNK分彆下降瞭26.3％及15.0％(t=0.77、0.61,均P＜0.01);p-IRS-1/IRS-1分彆下降瞭23.5％及29.4％(t=0.61、0.46,均P＜0.01),p-Akt/Akt則上升瞭43.7％及42.3％(t=-0.50、-0.28,均P＜0.01).但津力達組與二甲雙胍組之間差異均無統計學意義.結論 津力達顆粒可顯著提高IR大鼠的胰島素敏感性,其機製可能是津力達顆粒增彊瞭IR大鼠肝髒的抗氧化能力,抑製肝髒組織中JNK及IRS-1的燐痠化,增加瞭Akt的活性,從而改善胰島素信號的轉導.
목적 관찰중약진력체과립대고지음식유도적이도소저항(IR)모형대서간장양화응격급이도소신호통로적영향.방법 장36지6～8주령웅성SD대서여이고지사료위양12주유도IR모형,26지성모대서수궤수자법분위고지조(n=8)、진력체조(n=9)、이갑쌍고조(n=9),여이고지사료위양,동시이건강SD대서설립보식조(n=9).약물간예10주후행복강주사포도당내량시험(IPGTT)측취0、60、120 min혈당급이도소수평,계산은태모형IR지수(HOMA-IR)평개간장IR,이도소민감지수(ISI)평개전신이도소민감성,동시측정각조대서간장조직중초양화물기화매(SOD)、병이철(MDA)、환원형곡광감태(GSH)급과양화경매(CAT)등양화지표표체.Western blotting법측정간장조직중c-Jun안기말단격매(JNK)、단백격매B(PKB/Akt)급이도소수체저물1(IRS-1)적활성변화.채용단인소방차분석진행다조간균수비교.결과 약물간예10주후,IPGTT실험결과현시,여고지조상비,보식조、진력체조、이갑쌍고조공복급찬후혈당급혈청이도소수평출현불동정도하강,기중재60、120 min혈당급0、120 min이도소수평상균존재통계학차이(t=1.76～ 5.03,균P＜0.05),HOMA-IR출현하강,ISI명현상승(t=-187.63 ～5 635.06,균P＜0.05);여고지조상비,이갑쌍고조、진력체조SOD활성분별승고료64.9％、64.4％(t=-3 831.41、-2 879.73,균P＜0.05);MDA강저료36.3％급28.1％(t=183.52、105.77,균P＜0.05);CAT화GSH분별상승료101.0％、41.5％ (t=21.47、-512.31,균P＜0.05)급111.0％、39.8％ (t=19.68、357.20,균P＜0.05);p-JNK/JNK분별하강료26.3％급15.0％(t=0.77、0.61,균P＜0.01);p-IRS-1/IRS-1분별하강료23.5％급29.4％(t=0.61、0.46,균P＜0.01),p-Akt/Akt칙상승료43.7％급42.3％(t=-0.50、-0.28,균P＜0.01).단진력체조여이갑쌍고조지간차이균무통계학의의.결론 진력체과립가현저제고IR대서적이도소민감성,기궤제가능시진력체과립증강료IR대서간장적항양화능력,억제간장조직중JNK급IRS-1적린산화,증가료Akt적활성,종이개선이도소신호적전도.
Objective To investigate the effect ofJin Lida Granule (JLG) on the oxidative stress and insulin signaling in liver of insulin resistance(IR) rat induced by high-fat diet.Methods A group of 6-8 weeks male Sprague-Dawley (SD) rats were induced as IR models by high-fat food.Then IR rats were randomly divided into high-fat group (n=8),JLG group (n=9) and metformin group (n=9) by random number table.A paired normal-diet group was set up as a control.After ten weeks' treatment,intraperitoneal glucose tolerance test(IPGTT) was performed to measure the levels of serum glucose and insulin at 0,60 and 120 min.homeostasis model assessment of IR(HOMA-IR) and insulin sensitive index (ISI) were calculated to evaluate the state of IR in liver and whole body,respectively.The level of superoxide dismutase (SOD),malondialdehyde (MDA),glutathione (GSH),catalase (CAT) in liver tissues were measured; besides,the serine phosphorylation of insulin receptor substrate-1(IRS-1) and c-Jun N-terminal kinase(JNK),and the tyrosine phosphorylation of protein kinase B (Akt) were evaluated by Western blotting.The single factor ANOVA was used for data analysis.Results In the IPGTT after 10-week intervene,compared with high-fat group,JLG group,metformin group and control group showed a decreased level of fasting serum glucose,postprandial serum glucose and insulin,with a statistical significance in the serum glucose at 60 min and 120 min,and in the insulin at 0 min and 120 min (t=1.76-5.03,all P＜0.05); the HOMA-IR attenuated and ISI increased significantly in the JLG group,metformin group and control group(t=-187.63-5 635.06,all P＜ 0.05).Compared with those in high-fat group,the SOD increased for 64.9％ and 64.4％,the MDA decreased for 36.3％ and 28.1％,the CAT increased for 101.0％ and 41.5％,the GSH increased for 111.0％ and 39.8 ％,the p-JNK/JNK decreased for 26.3％ and 15.0％,the p-IRS-1/IRS-1 decreaed for 23.5％ and 29.4％ and the p-Akt/Akt increased for 43.7％ and 42.3％,respectively in the JLG group and metformin group (t=-0.50,-0.28,all P＜0.01).However,there was no significant difference between JLG group and metformin group.Conclusion JLG obviously improves the insulin sensitivity in rats.The pharmaceutical mechanisms maybe closely associated with the antioxidant capacity,as well as the improvement of insulin signaling transduction in liver including the elevated phosphorylation of Akt,and the reduced phosphorylation of JNK and IRS-1.
