中华糖尿病杂志
中華糖尿病雜誌
중화당뇨병잡지
CHINES JOURNAL OF DLABETES MELLITUS
2013年
11期
683-688
,共6页
俞媛贤%郭志新%齐伟%杜时晶%刘晋津%吴杰萍
俞媛賢%郭誌新%齊偉%杜時晶%劉晉津%吳傑萍
유원현%곽지신%제위%두시정%류진진%오걸평
糖尿病,1型%糖尿病心肌病%胰高血糖素样肽1
糖尿病,1型%糖尿病心肌病%胰高血糖素樣肽1
당뇨병,1형%당뇨병심기병%이고혈당소양태1
Diabetes mellitus,type 1%Diabetic cardiomyopathies%Glucagon-like peptide-1
目的 探讨胰高血糖素样肽1 (GLP-1)对1型糖尿病大鼠心肌组织烟酰胺腺嘌呤二核苷酸(NADPH)氧化酶亚单位p22phox和Nox4表达的影响.方法 将42只雄性SD大鼠用随机数字表法分为正常对照组(NC组,n=7)和糖尿病造模组(n=35).采用链脲佐菌素(STZ)对糖尿病造模组制备1型糖尿病大鼠模型.将造模成功的29只1型糖尿病大鼠用随机数字表法分为糖尿病组(DM组,n=10),糖尿病GLP-1低剂量治疗组(DL组,n=10)和糖尿病GLP-1高剂量治疗组(DH组,n=9).DL组予以艾塞那肽1μg/kg,2次/d皮下注射,DH组予以艾塞那肽5μg/kg,2次/d皮下注射.艾塞那肽治疗8周后处死动物.用实时荧光定量聚合酶链反应测定4组大鼠心肌p22phox和Nox4 mRNA的表达,免疫组化法检测心肌铜-锌-超氧化物歧化酶(Cu-Zn-SOD)蛋白表达.多组比较采用单因素方差分析.结果 与NC组比较,DM组大鼠心肌p22phox和Nox4 mRNA表达显著升高(t=5.77、5.36,均P＜0.05),心肌Cu-Zn-SOD蛋白表达显著升高(t=59.91,P＜0.05).艾塞那肽治疗8周后,与DM组比较,DL组和DH组大鼠心肌p22phox和Nox4 mRNA表达均显著降低(t=16.86、7.66和16.11、7.59,均P＜0.05),心肌Cu-Zn-SOD蛋白表达均显著降低(t=56.00、47.05,均P＜0.05).与DL组比较,DH组大鼠心肌p22phox和Nox4 mRNA表达显著降低(t=10.14、8.67,均P ＜0.05),而心肌Cu-Zn-SOD表达无明显变化(=81.91,P＞0.05).结论 GLP-1可剂量依赖性地下调1型糖尿病大鼠心肌p22phox和Nox4的表达,非剂量依赖性地上调心肌Cu-Zn-SOD表达,减轻氧化应激对心肌的损害,对糖尿病大鼠心肌产生保护作用.
目的 探討胰高血糖素樣肽1 (GLP-1)對1型糖尿病大鼠心肌組織煙酰胺腺嘌呤二覈苷痠(NADPH)氧化酶亞單位p22phox和Nox4錶達的影響.方法 將42隻雄性SD大鼠用隨機數字錶法分為正常對照組(NC組,n=7)和糖尿病造模組(n=35).採用鏈脲佐菌素(STZ)對糖尿病造模組製備1型糖尿病大鼠模型.將造模成功的29隻1型糖尿病大鼠用隨機數字錶法分為糖尿病組(DM組,n=10),糖尿病GLP-1低劑量治療組(DL組,n=10)和糖尿病GLP-1高劑量治療組(DH組,n=9).DL組予以艾塞那肽1μg/kg,2次/d皮下註射,DH組予以艾塞那肽5μg/kg,2次/d皮下註射.艾塞那肽治療8週後處死動物.用實時熒光定量聚閤酶鏈反應測定4組大鼠心肌p22phox和Nox4 mRNA的錶達,免疫組化法檢測心肌銅-鋅-超氧化物歧化酶(Cu-Zn-SOD)蛋白錶達.多組比較採用單因素方差分析.結果 與NC組比較,DM組大鼠心肌p22phox和Nox4 mRNA錶達顯著升高(t=5.77、5.36,均P＜0.05),心肌Cu-Zn-SOD蛋白錶達顯著升高(t=59.91,P＜0.05).艾塞那肽治療8週後,與DM組比較,DL組和DH組大鼠心肌p22phox和Nox4 mRNA錶達均顯著降低(t=16.86、7.66和16.11、7.59,均P＜0.05),心肌Cu-Zn-SOD蛋白錶達均顯著降低(t=56.00、47.05,均P＜0.05).與DL組比較,DH組大鼠心肌p22phox和Nox4 mRNA錶達顯著降低(t=10.14、8.67,均P ＜0.05),而心肌Cu-Zn-SOD錶達無明顯變化(=81.91,P＞0.05).結論 GLP-1可劑量依賴性地下調1型糖尿病大鼠心肌p22phox和Nox4的錶達,非劑量依賴性地上調心肌Cu-Zn-SOD錶達,減輕氧化應激對心肌的損害,對糖尿病大鼠心肌產生保護作用.
목적 탐토이고혈당소양태1 (GLP-1)대1형당뇨병대서심기조직연선알선표령이핵감산(NADPH)양화매아단위p22phox화Nox4표체적영향.방법 장42지웅성SD대서용수궤수자표법분위정상대조조(NC조,n=7)화당뇨병조모조(n=35).채용련뇨좌균소(STZ)대당뇨병조모조제비1형당뇨병대서모형.장조모성공적29지1형당뇨병대서용수궤수자표법분위당뇨병조(DM조,n=10),당뇨병GLP-1저제량치료조(DL조,n=10)화당뇨병GLP-1고제량치료조(DH조,n=9).DL조여이애새나태1μg/kg,2차/d피하주사,DH조여이애새나태5μg/kg,2차/d피하주사.애새나태치료8주후처사동물.용실시형광정량취합매련반응측정4조대서심기p22phox화Nox4 mRNA적표체,면역조화법검측심기동-자-초양화물기화매(Cu-Zn-SOD)단백표체.다조비교채용단인소방차분석.결과 여NC조비교,DM조대서심기p22phox화Nox4 mRNA표체현저승고(t=5.77、5.36,균P＜0.05),심기Cu-Zn-SOD단백표체현저승고(t=59.91,P＜0.05).애새나태치료8주후,여DM조비교,DL조화DH조대서심기p22phox화Nox4 mRNA표체균현저강저(t=16.86、7.66화16.11、7.59,균P＜0.05),심기Cu-Zn-SOD단백표체균현저강저(t=56.00、47.05,균P＜0.05).여DL조비교,DH조대서심기p22phox화Nox4 mRNA표체현저강저(t=10.14、8.67,균P ＜0.05),이심기Cu-Zn-SOD표체무명현변화(=81.91,P＞0.05).결론 GLP-1가제량의뢰성지하조1형당뇨병대서심기p22phox화Nox4적표체,비제량의뢰성지상조심기Cu-Zn-SOD표체,감경양화응격대심기적손해,대당뇨병대서심기산생보호작용.
Objective To explore the effect of glucagon-like peptide-1 on the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22phox and Nox4 in the heart tissue of type 1 diabetic rats.Methods Forty-two male Sprague-Dawley(SD) rats were randomly divided into normal control group (group A,n=7) and diabetic model group (n =35) with the random number table.Type 1 diabetic model was established by intraperitoneal injection of streptozotocin.Twenty-nine successfully-induced diabetic rats were randomly divided into diabetic (group DM,n =10),diabetic treated with low-dose of GLP-1 (group DL,n =10) and diabetic treated with high-dose of GLP-1 (group DH,n =9) with the random number table method.The rats in group DL were given exenatide in dose of 1 μg/kg twice daily by subcutaneous injection.The rats in group DH were given exenatide in dose of 5 μg/kg twice daily by subcutaneous injection.All rats were sacrificed after exenatide treatment for eight weeks.The mRNA expression of myocardial p22phox and Nox4 in the rats of four groups was detected by real-time fluorescence quantitative polymerase chain reaction(PCR),and the protein expression of myocardial copper zinc-superoxide dismutase (Cu-Zn-SOD) was detected by immunohistochemical staining.Statistical analysis among groups was performed by using one way ANOVA.Results Compared with group NC,the mRNA expression of myocardial p22phox and Nox4 and the myocardial Cu-Zn-SOD protein expression increased significantly in group DM(t =5.77,5.36,59.91,all P ＜0.05).After exenatide treatment for 8 weeks,the mRNA expression of myocardial p22phox and Nox4 and the myocardial Cu-Zn-SOD protein expression decreased significantly in group DL and DH (t =16.86,7.66 and 16.11,7.59 and 56.00,47.05,and all P ＜ 0.05).Compared with group DL,the mRNA expression of myocardial p22phox and Nox4 decreased significantly in group DH (t =10.14,8.67,both P ＜ 0.05).There was no significant difference in the expression of myocardial Cu-Zn-SOD between group DL and group DH (t =81.91,P ＞ 0.05).Conclusions GLP-1 can dose-dependently down-regulate the over-expression of myocardial Nox4 and p22phox mRNA,and dose-independently up-regulate the expression of myocardial Cu-Zn-SOD in type 1 diabetic rats,which may lessen the myocardial damage induced by oxidative stress.
