CAJ | 학술논문

目的动态研究2型糖尿病大鼠肝脏脂质代谢紊乱所致的损伤和细胞凋亡及其与固醇调节组件结合蛋白-1c(SREBP-1c)及C Jun氨基端激酶(JNK)表达的关系. 方法试验大鼠分为4组:(1)糖尿病组,64只,用高糖高脂饲料喂养,予链脲佐菌素(STZ)30 mg/kg个次性腹腔注射复制糖尿病模型；(2)正常对照组,37只,饲以普通饲料,腹腔注射柠檬酸盐缓冲液；(3)STZ组,42只,饲以普通饲料,腹腔注射STZ;(4)高糖高脂组,37只,饲以高糖高脂饲料,腹腔注射柠檬酸盐缓冲液.在不同阶段抽样检查动物体质量、肝质量、空腹血糖、空腹胰岛素(FINS)、三酰甘油(TG)、总胆固醇(TC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)；观察肝脏病理组织学变化及超微结构变化；用实时荧光定量PCR技术检测SREBP-1c、JNK蛋白及mRNA的表达；用流式细胞术检测肝脏细胞凋亡.比较不同组间的差异. 结果(1)糖尿病组大鼠体质量比正常对照组、STZ组、高糖高脂组明显下降(P＜0.05),肝质量则明显上升(P＜0.05)；糖尿病组大鼠空腹血糖、FINS、TG、TC、ALT、AST亦明显升高(P＜0.05).光镜下见肝细胞脂肪变性、炎性细胞浸润,网状纤维增多；电镜显示细胞器结构紊乱,随着病程延长病变逐渐加重,肝细胞凋亡增高；SREBP-1c、JNK蛋白及mRNA的表达增高.(2)高糖高脂组亦呈类似的肝脏病变及SREBP-1c、JNK蛋白及mRNA的表达增高的改变,但程度较轻. 结论胰岛素抵抗和高血糖可导致糖尿病肝脏病变；2型糖尿病、SREBP-1c、JNK表达升高参与了肝脏脂质代谢紊乱与细胞凋亡.
목적 동태연구2형당뇨병대서간장지질대사문란소치적손상화세포조망급기여고순조절조건결합단백-1c(SREBP-1c)급C Jun안기단격매(JNK)표체적관계. 방법 시험대서분위4조:(1)당뇨병조,64지,용고당고지사료위양,여련뇨좌균소(STZ)30 mg/kg개차성복강주사복제당뇨병모형；(2)정상대조조,37지,사이보통사료,복강주사저몽산염완충액；(3)STZ조,42지,사이보통사료,복강주사STZ;(4)고당고지조,37지,사이고당고지사료,복강주사저몽산염완충액.재불동계단추양검사동물체질량、간질량、공복혈당、공복이도소(FINS)、삼선감유(TG)、총담고순(TC)、곡병전안매(ALT)、곡초전안매(AST)；관찰간장병리조직학변화급초미결구변화；용실시형광정량PCR기술검측SREBP-1c、JNK단백급mRNA적표체；용류식세포술검측간장세포조망.비교불동조간적차이. 결과(1)당뇨병조대서체질량비정상대조조、STZ조、고당고지조명현하강(P＜0.05),간질량칙명현상승(P＜0.05)；당뇨병조대서공복혈당、FINS、TG、TC、ALT、AST역명현승고(P＜0.05).광경하견간세포지방변성、염성세포침윤,망상섬유증다；전경현시세포기결구문란,수착병정연장병변축점가중,간세포조망증고；SREBP-1c、JNK단백급mRNA적표체증고.(2)고당고지조역정유사적간장병변급SREBP-1c、JNK단백급mRNA적표체증고적개변,단정도교경. 결론 이도소저항화고혈당가도치당뇨병간장병변；2형당뇨병、SREBP-1c、JNK표체승고삼여료간장지질대사문란여세포조망.
Objective To study the dynamic changes of injury and apoptosis of liver induced by lipid metabolic disturbance in the rats with diabetes mellitus and their correlation with the expressions of sterol regulatory element binding protein-1c(SREBP-1c)and c-Jun N-terminal kinase(JNK).Methods Experimental animals were randomly divided into 4 groups:diabetesgroup(n=64)induced by high-carbohydrate and high-fat diet plus intra-peritoneal streptozeotocin(STZ)injection,normal control(n=37)fed regular diet and receiving citric buffer solution injection,STZ group(n=42)fed regular diet and receiving STZ injection,high gluaxeard fat group(n =37)receiving citric buffer solution injection.Body weight,liver weight,fasting plasma glucose(FPG),fasting insulin(FINS),triglyceride(TG),total cholesterole(TC),alanine transaminase(ALT),asparate transaminase(AST)were detected at various time intervals.The changes of liver histopathology and ultrastructure were observed by ES and Sudan Ⅲ stanings,transmission electrom microscope.The expressions of SREBP-1c and JNK mRNAs and proteins were determined by real time-PCR methods.Apoptosis was analyzed by flow cytometry.Results The diabetic rats showed much lower body weight(P＜0.05)and higher liver weight than controls,STZ group and high-carbohydrate and fat group(P＜0.05),while showed higher levels(P＜0.05)of serum FPG,FINS,TG,TC,ALT,AST.Diabetic rats exhibited fatty degeneration of liver cells accompanied by inflammatory infiltration and fibrosis.Organelle structures were more disturbed and apoptosis was more obviou along with longer course of disease.The expressions of SREBP-1c,JNK proteins and mRNA were significantly enhanced.The rats fed high-carbohydrate and fat diet also showed similar liver lesions and enhanced SREBP-1c,J NK proteins and mRNA expressions but not as severe as in diabetes group Conclusions Insulin resistance and high blood glucose may induce diabetic hepatopathy.The high expressions of JNK and SREBP-1c may play important roles in liver lipid metabolism disorders and cell apoptosis.