中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2015年
4期
690-694
,共5页
胰高血糖素样肽1%非酒精性脂肪肝%胰岛素抵抗%蛋白激酶Cε
胰高血糖素樣肽1%非酒精性脂肪肝%胰島素牴抗%蛋白激酶Cε
이고혈당소양태1%비주정성지방간%이도소저항%단백격매Cε
Glucagon-like peptide 1%Non-alcoholic fatty liver disease%Insulin resistance%Protein kinase Cε
目的：探讨胰高血糖素样肽1（ GLP-1）对非酒精性脂肪肝病SD大鼠的治疗作用及可能的机制。方法：32只SPF级雄性SD大鼠（体重约130 g）随机抽取21只予高脂饮食（88％普通饲料＋10％猪油＋2％胆固醇），余下11只予普通饲料饮食作为空白对照组；12周后，将高脂饮食大鼠随机分为2组，每组10只：高脂组予高脂饮食并腹腔注射等体积的无菌生理盐水，治疗组予高脂饮食并腹腔注射利拉鲁肽（ GLP-1类似物）注射液（0.6 mg· kg－1· d－1）。治疗4周后处死全部大鼠抽取静脉血并取肝脏组织。全自动生化仪检测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、甘油三酯（TG）、总胆固醇（TC）及葡萄糖（GLU）含量；ELISA法测定血清胰岛素含量。石蜡包埋肝组织做病理切片及HE染色；real-time PCR法测定肝组织蛋白激酶Cε（ PKCε） mRNA的表达，Western blot测定肝组织胞浆PKCε蛋白表达。结果：与正常对照组相比，高脂组的ALT、AST、TG、TC、胰岛素抵抗指数及肝脂数均明显升高；GLP-1治疗组与高脂组相比ALT、AST、TG、TC、胰岛素抵抗指数及肝脂数均下降，差异有统计学意义（P＜0.05）；real-time PCR及Western blot结果提示高脂组PKCεmRNA及蛋白表达减少（P＜0.05）；GLP-1治疗组PKCεmRNA及蛋白表达增多（ P＜0.05）。结论：GLP-1类似物可改善非酒精性脂肪肝的脂质代谢及胰岛素抵抗，该过程可能与PKCε有关。
目的：探討胰高血糖素樣肽1（ GLP-1）對非酒精性脂肪肝病SD大鼠的治療作用及可能的機製。方法：32隻SPF級雄性SD大鼠（體重約130 g）隨機抽取21隻予高脂飲食（88％普通飼料＋10％豬油＋2％膽固醇），餘下11隻予普通飼料飲食作為空白對照組；12週後，將高脂飲食大鼠隨機分為2組，每組10隻：高脂組予高脂飲食併腹腔註射等體積的無菌生理鹽水，治療組予高脂飲食併腹腔註射利拉魯肽（ GLP-1類似物）註射液（0.6 mg· kg－1· d－1）。治療4週後處死全部大鼠抽取靜脈血併取肝髒組織。全自動生化儀檢測血清穀丙轉氨酶（ALT）、穀草轉氨酶（AST）、甘油三酯（TG）、總膽固醇（TC）及葡萄糖（GLU）含量；ELISA法測定血清胰島素含量。石蠟包埋肝組織做病理切片及HE染色；real-time PCR法測定肝組織蛋白激酶Cε（ PKCε） mRNA的錶達，Western blot測定肝組織胞漿PKCε蛋白錶達。結果：與正常對照組相比，高脂組的ALT、AST、TG、TC、胰島素牴抗指數及肝脂數均明顯升高；GLP-1治療組與高脂組相比ALT、AST、TG、TC、胰島素牴抗指數及肝脂數均下降，差異有統計學意義（P＜0.05）；real-time PCR及Western blot結果提示高脂組PKCεmRNA及蛋白錶達減少（P＜0.05）；GLP-1治療組PKCεmRNA及蛋白錶達增多（ P＜0.05）。結論：GLP-1類似物可改善非酒精性脂肪肝的脂質代謝及胰島素牴抗，該過程可能與PKCε有關。
목적：탐토이고혈당소양태1（ GLP-1）대비주정성지방간병SD대서적치료작용급가능적궤제。방법：32지SPF급웅성SD대서（체중약130 g）수궤추취21지여고지음식（88％보통사료＋10％저유＋2％담고순），여하11지여보통사료음식작위공백대조조；12주후，장고지음식대서수궤분위2조，매조10지：고지조여고지음식병복강주사등체적적무균생리염수，치료조여고지음식병복강주사리랍로태（ GLP-1유사물）주사액（0.6 mg· kg－1· d－1）。치료4주후처사전부대서추취정맥혈병취간장조직。전자동생화의검측혈청곡병전안매（ALT）、곡초전안매（AST）、감유삼지（TG）、총담고순（TC）급포도당（GLU）함량；ELISA법측정혈청이도소함량。석사포매간조직주병리절편급HE염색；real-time PCR법측정간조직단백격매Cε（ PKCε） mRNA적표체，Western blot측정간조직포장PKCε단백표체。결과：여정상대조조상비，고지조적ALT、AST、TG、TC、이도소저항지수급간지수균명현승고；GLP-1치료조여고지조상비ALT、AST、TG、TC、이도소저항지수급간지수균하강，차이유통계학의의（P＜0.05）；real-time PCR급Western blot결과제시고지조PKCεmRNA급단백표체감소（P＜0.05）；GLP-1치료조PKCεmRNA급단백표체증다（ P＜0.05）。결론：GLP-1유사물가개선비주정성지방간적지질대사급이도소저항，해과정가능여PKCε유관。
AIM:To observe the therapeutic effect of glucagon-like peptide 1 (GLP-1) analog on nonalcoholic fatty liver disease of rats and to investigate the underlying mechanism.METHODS:SD rats (n=21) were used to estab-lish a nonalcoholic fatty liver disease model by feeding a high fat diet for 12 weeks, and other 11 rats were fed with a normal diet for 16 weeks.The model rats were randomly divided into 2 equal groups:one group was treated with glucagon-like pep-tide 1 analog (0.6 mg· kg-1 · d-1 ) by intraperitoneal injection for 4 weeks, the other group using saline as a control.Af-ter treatment, fasting blood glucose, serum insulin, blood lipids, liver function and the pathological changes of the hepatic tissues were evaluated and the expression of PKCεat mRNA and protein levels in the liver tissues was detected by real-time PCR and Western blot, respectively.RESULTS:Compared with model group, the intervention of GLP-1 significantly re-duced insulin resistance index (HOMA-IR), improved the liver function (P<0.05), decreased the liver index and blood lipids (P<0.05).HE staining showed obvious pathological changes of the hepatic tissues in model group, and the inter-vention of GLP-1 significantly reduced lipid droplets in the hepatocytes and improved the structural damage of the liver.The expression of hepatic protein kinase Cε( PKCε) at mRNA and protein levels significantly decreased which were reversed by treating with GLP-1.CONCLUSION:GLP-1 shows good therapeutic effect on nonalcoholic fatty liver disease of rats, pos-sibly by controlling lipid metabolism and reducing insulin resistance, which may be related to PKCεexpression.
