CAJ | 학술논문

1,25-二羟维生素D3%糖尿病,实验性%过氧化物酶增殖物激活受体-α%肝细胞核因子-4α%胆固醇调节元件结合蛋白-1C%载脂蛋白A5%甘油三酯 1,25-二羥維生素D3%糖尿病,實驗性%過氧化物酶增殖物激活受體-α%肝細胞覈因子-4α%膽固醇調節元件結閤蛋白-1C%載脂蛋白A5%甘油三酯
1,25-이간유생소D3%당뇨병,실험성%과양화물매증식물격활수체-α%간세포핵인자-4α%담고순조절원건결합단백-1C%재지단백A5%감유삼지
1,25-dihydroxyvitamin D3%Diabetes mellitus,experimental%Peroxisome proliferator-activated receptor α%Hepatocyte neclear factor-4α%Sterol regulatory element binding proteins-1C%Apolipoprotein A5%Triglyceride

目的活性维生素D与2型糖尿病、高脂血症的发生发展密切相关,通过观察1,25-二羟维生素D3[1,25(OH)2D3]对实验糖尿病大鼠模型肝脏中过氧化物酶增殖物激活受体-α(PPAR-α)、肝细胞核因子-4α(HNF-4α)、胆固醇调节元件结合蛋白-1C(SREBP-1C)、载脂蛋白A5(apoA5)表达及甘油三酯含量的影响,探讨1,25(OH)2D3调控肝脏甘油三酯的机制.方法取80只健康雄性Wistar大鼠,分成糖尿病组20只、1,25(OH)2D3干预组(VitD干预组)20只、PPAR-α抑制组20只和正常对照组20只.以随机数字表法,取各组大鼠各15只,心内取血检测生化指标,采用实时荧光定量PCR、Western印迹法分别对大鼠的肝脏组织中PPAR-α、HNF-4α、SREBP-1C、apoA5基因及蛋白表达水平进行检测,并用酶法检测肝脏组织中甘油三酯含量.结果 (1)糖尿病组肝脏中PPAR-α、HNF-4α、apoA5基因、蛋白表达较正常对照组显著降低(P＜0.05),而SREBP-1C基因、蛋白表达及甘油三酯含量较正常对照组显著增加(P＜0.05).(2)VitD干预组肝脏中PPAR-α、HNF-4α、apoA5基因及蛋白表达较糖尿病组明显增加(P＜0.05),而SREBP-1C基因及蛋白、甘油三酯含量较糖尿病组明显减少(P＜0.05).(3)VitD干预组肝脏中PPAR-α、HNF-4α、SREBP-1C、apoA5基因、蛋白表达、甘油三酯含量较正常对照组无显著性差异(P＞0.05).(4)PPAR-α抑制组PPAR-α、HNF-4α、apoA5基因、蛋白表达较正常对照组显著降低(P＜0.05),而SREBP-1C基因、蛋白表达、甘油三酯含量较正常对照组明显增加(P＜0.05).(5) PPAR-α抑制组PPAR-α基因、蛋白表达较糖尿病组显著降低(P＜0.05),而HNF-4α、apoA5、SREBP-1C基因、蛋白表达及甘油三酯含量与糖尿病组无显著性差异(P＜0.05).(6) PPAR-α抑制组PPAR-α、HNF-4α、apoA5基因、蛋白表达较VitD干预组显著降低(P＜0.05),而SREBP-1C基因、蛋白表达及甘油三酯含量较VitD干预组显著增加(P＜0.05).结论 1,25(OH)2D3可能通过上调肝脏中PPAR-α、HNF-4α、apoA5表达,抑制SREBP-1C的表达,从而降低甘油三酯水平. 目的活性維生素D與2型糖尿病、高脂血癥的髮生髮展密切相關,通過觀察1,25-二羥維生素D3[1,25(OH)2D3]對實驗糖尿病大鼠模型肝髒中過氧化物酶增殖物激活受體-α(PPAR-α)、肝細胞覈因子-4α(HNF-4α)、膽固醇調節元件結閤蛋白-1C(SREBP-1C)、載脂蛋白A5(apoA5)錶達及甘油三酯含量的影響,探討1,25(OH)2D3調控肝髒甘油三酯的機製.方法取80隻健康雄性Wistar大鼠,分成糖尿病組20隻、1,25(OH)2D3榦預組(VitD榦預組)20隻、PPAR-α抑製組20隻和正常對照組20隻.以隨機數字錶法,取各組大鼠各15隻,心內取血檢測生化指標,採用實時熒光定量PCR、Western印跡法分彆對大鼠的肝髒組織中PPAR-α、HNF-4α、SREBP-1C、apoA5基因及蛋白錶達水平進行檢測,併用酶法檢測肝髒組織中甘油三酯含量.結果 (1)糖尿病組肝髒中PPAR-α、HNF-4α、apoA5基因、蛋白錶達較正常對照組顯著降低(P＜0.05),而SREBP-1C基因、蛋白錶達及甘油三酯含量較正常對照組顯著增加(P＜0.05).(2)VitD榦預組肝髒中PPAR-α、HNF-4α、apoA5基因及蛋白錶達較糖尿病組明顯增加(P＜0.05),而SREBP-1C基因及蛋白、甘油三酯含量較糖尿病組明顯減少(P＜0.05).(3)VitD榦預組肝髒中PPAR-α、HNF-4α、SREBP-1C、apoA5基因、蛋白錶達、甘油三酯含量較正常對照組無顯著性差異(P＞0.05).(4)PPAR-α抑製組PPAR-α、HNF-4α、apoA5基因、蛋白錶達較正常對照組顯著降低(P＜0.05),而SREBP-1C基因、蛋白錶達、甘油三酯含量較正常對照組明顯增加(P＜0.05).(5) PPAR-α抑製組PPAR-α基因、蛋白錶達較糖尿病組顯著降低(P＜0.05),而HNF-4α、apoA5、SREBP-1C基因、蛋白錶達及甘油三酯含量與糖尿病組無顯著性差異(P＜0.05).(6) PPAR-α抑製組PPAR-α、HNF-4α、apoA5基因、蛋白錶達較VitD榦預組顯著降低(P＜0.05),而SREBP-1C基因、蛋白錶達及甘油三酯含量較VitD榦預組顯著增加(P＜0.05).結論 1,25(OH)2D3可能通過上調肝髒中PPAR-α、HNF-4α、apoA5錶達,抑製SREBP-1C的錶達,從而降低甘油三酯水平.
목적 활성유생소D여2형당뇨병、고지혈증적발생발전밀절상관,통과관찰1,25-이간유생소D3[1,25(OH)2D3]대실험당뇨병대서모형간장중과양화물매증식물격활수체-α(PPAR-α)、간세포핵인자-4α(HNF-4α)、담고순조절원건결합단백-1C(SREBP-1C)、재지단백A5(apoA5)표체급감유삼지함량적영향,탐토1,25(OH)2D3조공간장감유삼지적궤제.방법 취80지건강웅성Wistar대서,분성당뇨병조20지、1,25(OH)2D3간예조(VitD간예조)20지、PPAR-α억제조20지화정상대조조20지.이수궤수자표법,취각조대서각15지,심내취혈검측생화지표,채용실시형광정량PCR、Western인적법분별대대서적간장조직중PPAR-α、HNF-4α、SREBP-1C、apoA5기인급단백표체수평진행검측,병용매법검측간장조직중감유삼지함량.결과 (1)당뇨병조간장중PPAR-α、HNF-4α、apoA5기인、단백표체교정상대조조현저강저(P＜0.05),이SREBP-1C기인、단백표체급감유삼지함량교정상대조조현저증가(P＜0.05).(2)VitD간예조간장중PPAR-α、HNF-4α、apoA5기인급단백표체교당뇨병조명현증가(P＜0.05),이SREBP-1C기인급단백、감유삼지함량교당뇨병조명현감소(P＜0.05).(3)VitD간예조간장중PPAR-α、HNF-4α、SREBP-1C、apoA5기인、단백표체、감유삼지함량교정상대조조무현저성차이(P＞0.05).(4)PPAR-α억제조PPAR-α、HNF-4α、apoA5기인、단백표체교정상대조조현저강저(P＜0.05),이SREBP-1C기인、단백표체、감유삼지함량교정상대조조명현증가(P＜0.05).(5) PPAR-α억제조PPAR-α기인、단백표체교당뇨병조현저강저(P＜0.05),이HNF-4α、apoA5、SREBP-1C기인、단백표체급감유삼지함량여당뇨병조무현저성차이(P＜0.05).(6) PPAR-α억제조PPAR-α、HNF-4α、apoA5기인、단백표체교VitD간예조현저강저(P＜0.05),이SREBP-1C기인、단백표체급감유삼지함량교VitD간예조현저증가(P＜0.05).결론 1,25(OH)2D3가능통과상조간장중PPAR-α、HNF-4α、apoA5표체,억제SREBP-1C적표체,종이강저감유삼지수평.
Objective Activity of vitamin D is correlated with type 2 diabetes mellitus and hyperlipidemia,but the concrete relationship of 1,25-dihydroxyvitamin D3 [1,25 (OH) 2 D3] and triglyceride is unknown.This study was to observe the gene and protein expression of peroxisome proliferator-activated receptor α(PPAR-α),hepatocyte neclear factor-4α (HNF-4α),sterol regulatory element binding proteins-1C (SREBP-1 C),apolipoprotein (apoA5) during 1,25 (OH)2D3 regulation of triglyceride in liver of diabetes rat,as well as to investigate the mechanism of 1,25 (OH) 2D3 in influencing triglyceride in liver.Methods Eighty male Wistar Rats were divided into 4 groups:20 rats with diabetes mellitus(DM group),20 rats of 1,25 (OH)2D3 treated group (V itD group),20 rats with PPAR-α inhibition group,and 20 rats of normal control group.15 from each group were taken in random by random number table to detect biochemical indicators and to detect the gene and protein expressions of PPAR-α,HNF-4α,SREBP-1 C,apoA5 in liver,using realtime-fluorescent quantitation reverse transcription,polymerase chain reaction and Western blot.The level of triglyceride in liver was also detected.Results (1) The gene and protein expression of PPAR-α,HNF-4α,apoA5 in liver of diabetic rat was lower than that in normal control group (P ＜ 0.05).The expression of SREBP-1C and the level of triglyceride in liver of diabetic rat were higher than those of normal control group (P＜0.05).(2)The expression of PPAR-α,HNF-4α,apoA5 in liver of VitD group were higher than those of DM group(P＜0.05).The gene and protein expression of SREBP-1C and the level of triglyceride in VitD group were lower than those in DM group(P＜0.05).(3) The expression of PPAR-α,HNF-4α,SREBP-1 C,apoA5,and the level of triglyceride showed no significant difference between VitD group and normal control group(P＞0.05).(4) The expression of PPAR-α,HNF-4α,and apoA5 in liver of PPAR-α inhibition group was lower than that in normal control group(P＜0.05).The expression of SREBP-1C and the level of triglyceride in liver of PPAR-α inhibition group were higher than those in normal control group(P＜0.05).(5) The expression of PPAR-α in liver of PPAR-α inhibition group was lower than that in diabetic rat (P＜0.05).The expression of HNF-4α,apoA5,SREBP-1 C,and the level of triglyceride showed no significant difference between PPAR-α inhibition group and diabetic rat(P＞0.05).(6) The expression of PPAR-α,HNF-4α,apoA5 in liver of PPAR-α inhibition group was lower than that in VitD group(P＜ 0.05).The expression of SREBP-1C and the level of triglyceride in liver of PPAR-α inhibition group were higher than those in VitD group (P ＜ 0.05).Conclusions 1,25 (OH) 2D3 may lower the level of serum triglyceride by upregulating the expression of PPAR-α,HNF-4α,and apoA5 and inhibiting the expression of SREBP-1C in liver.