CAJ | 학술논문

目的观察脂联素对普通大鼠和糖尿病大鼠脑缺血再灌注(ischemic-reperfusion injury,I/R)损伤的神经保护作用,并探讨其可能的作用机制.方法雄性SPF级SD大鼠64只,随机数字表法分为普通组(C组,32只)、2型糖尿病组(D组,32只),C组给予普通饲料喂养,D组采用高脂高糖饮食法制备2型糖尿病模型.两组大鼠再行大脑中动脉闭塞造模,各分为脂联素干预组(CAPN、DAPN)、空白干预组(C0、D0)4个亚组,每个亚组16只,脂联素干预组在I/R损伤后lh时经颈静脉注射重组球形脂联素5 μg,空白干预组在相同时间点经颈静脉注射等体积生理盐水.测量各组大鼠体重,采用血糖试纸条法检测各组大鼠缺血前血糖判断糖尿病造模情况；脂联素干预24 h后,Longa评分法评估大鼠神经功能变化,每个亚组中对8只大鼠行HE染色,观察脑I/R损伤区细胞形态学变化；脂联素干预后2周,每个亚组的剩余8只大鼠用三维激光共聚焦显微镜图像分析法,检测I/R损伤区血管密度的变化.结果 D组大鼠体重低于C组[(284.06±19.85)与(220.31 ±21.87)g,t=8.634,P=0.000],缺血前血糖高于C组[(4.36±0.13)与(22.92±1.58) mmol/L,t=11.74,P=0.000]；脂联素显著降低C组[(2.29±0.69)与(1.70±0.68)分,t=2.186,P=0.038]、D组[(2.89±0.33)与(2.40±0.51)分,t=2.567,P=0.018]大鼠的神经功能评分.HE染色观察,脂联素干预后,普通组、糖尿病组大鼠神经元破坏较相应空白干预组明显减轻.脂联素显著增加C组[(2014.58±61.18)/0.002 mm2与(3211.95±71.64)/0.002 mm2,t=12.16,P=0.023]、D组[(502.86±30.43)/0.002 mm2与(1426.69±97.24)/0.002mm2,=25.64,P=0.001] I/R损伤区皮质的血管密度；脂联素显著增加C组[(472.59 ±4.78)/0.002 mm2与(736.60±104.90)/0.002mm2,t=7.11,P=0.007]、D组[(432.04±4.65)/0.002 mm2与(1780.75±74.54)/0.002 mm2,t=51.078,P=0.000] I/R损伤区纹状体的血管密度.结论脂联素对普通大鼠、糖尿病大鼠脑I/R损伤发挥神经保护作用,减轻脑组织I/R损伤程度,其可能的作用机制是促进脑I/R损伤区血管修复、再生. 目的觀察脂聯素對普通大鼠和糖尿病大鼠腦缺血再灌註(ischemic-reperfusion injury,I/R)損傷的神經保護作用,併探討其可能的作用機製.方法雄性SPF級SD大鼠64隻,隨機數字錶法分為普通組(C組,32隻)、2型糖尿病組(D組,32隻),C組給予普通飼料餵養,D組採用高脂高糖飲食法製備2型糖尿病模型.兩組大鼠再行大腦中動脈閉塞造模,各分為脂聯素榦預組(CAPN、DAPN)、空白榦預組(C0、D0)4箇亞組,每箇亞組16隻,脂聯素榦預組在I/R損傷後lh時經頸靜脈註射重組毬形脂聯素5 μg,空白榦預組在相同時間點經頸靜脈註射等體積生理鹽水.測量各組大鼠體重,採用血糖試紙條法檢測各組大鼠缺血前血糖判斷糖尿病造模情況；脂聯素榦預24 h後,Longa評分法評估大鼠神經功能變化,每箇亞組中對8隻大鼠行HE染色,觀察腦I/R損傷區細胞形態學變化；脂聯素榦預後2週,每箇亞組的剩餘8隻大鼠用三維激光共聚焦顯微鏡圖像分析法,檢測I/R損傷區血管密度的變化.結果 D組大鼠體重低于C組[(284.06±19.85)與(220.31 ±21.87)g,t=8.634,P=0.000],缺血前血糖高于C組[(4.36±0.13)與(22.92±1.58) mmol/L,t=11.74,P=0.000]；脂聯素顯著降低C組[(2.29±0.69)與(1.70±0.68)分,t=2.186,P=0.038]、D組[(2.89±0.33)與(2.40±0.51)分,t=2.567,P=0.018]大鼠的神經功能評分.HE染色觀察,脂聯素榦預後,普通組、糖尿病組大鼠神經元破壞較相應空白榦預組明顯減輕.脂聯素顯著增加C組[(2014.58±61.18)/0.002 mm2與(3211.95±71.64)/0.002 mm2,t=12.16,P=0.023]、D組[(502.86±30.43)/0.002 mm2與(1426.69±97.24)/0.002mm2,=25.64,P=0.001] I/R損傷區皮質的血管密度；脂聯素顯著增加C組[(472.59 ±4.78)/0.002 mm2與(736.60±104.90)/0.002mm2,t=7.11,P=0.007]、D組[(432.04±4.65)/0.002 mm2與(1780.75±74.54)/0.002 mm2,t=51.078,P=0.000] I/R損傷區紋狀體的血管密度.結論脂聯素對普通大鼠、糖尿病大鼠腦I/R損傷髮揮神經保護作用,減輕腦組織I/R損傷程度,其可能的作用機製是促進腦I/R損傷區血管脩複、再生.
목적 관찰지련소대보통대서화당뇨병대서뇌결혈재관주(ischemic-reperfusion injury,I/R)손상적신경보호작용,병탐토기가능적작용궤제.방법 웅성SPF급SD대서64지,수궤수자표법분위보통조(C조,32지)、2형당뇨병조(D조,32지),C조급여보통사료위양,D조채용고지고당음식법제비2형당뇨병모형.량조대서재행대뇌중동맥폐새조모,각분위지련소간예조(CAPN、DAPN)、공백간예조(C0、D0)4개아조,매개아조16지,지련소간예조재I/R손상후lh시경경정맥주사중조구형지련소5 μg,공백간예조재상동시간점경경정맥주사등체적생리염수.측량각조대서체중,채용혈당시지조법검측각조대서결혈전혈당판단당뇨병조모정황；지련소간예24 h후,Longa평분법평고대서신경공능변화,매개아조중대8지대서행HE염색,관찰뇌I/R손상구세포형태학변화；지련소간예후2주,매개아조적잉여8지대서용삼유격광공취초현미경도상분석법,검측I/R손상구혈관밀도적변화.결과 D조대서체중저우C조[(284.06±19.85)여(220.31 ±21.87)g,t=8.634,P=0.000],결혈전혈당고우C조[(4.36±0.13)여(22.92±1.58) mmol/L,t=11.74,P=0.000]；지련소현저강저C조[(2.29±0.69)여(1.70±0.68)분,t=2.186,P=0.038]、D조[(2.89±0.33)여(2.40±0.51)분,t=2.567,P=0.018]대서적신경공능평분.HE염색관찰,지련소간예후,보통조、당뇨병조대서신경원파배교상응공백간예조명현감경.지련소현저증가C조[(2014.58±61.18)/0.002 mm2여(3211.95±71.64)/0.002 mm2,t=12.16,P=0.023]、D조[(502.86±30.43)/0.002 mm2여(1426.69±97.24)/0.002mm2,=25.64,P=0.001] I/R손상구피질적혈관밀도；지련소현저증가C조[(472.59 ±4.78)/0.002 mm2여(736.60±104.90)/0.002mm2,t=7.11,P=0.007]、D조[(432.04±4.65)/0.002 mm2여(1780.75±74.54)/0.002 mm2,t=51.078,P=0.000] I/R손상구문상체적혈관밀도.결론 지련소대보통대서、당뇨병대서뇌I/R손상발휘신경보호작용,감경뇌조직I/R손상정도,기가능적작용궤제시촉진뇌I/R손상구혈관수복、재생.
Objective To investigate the neuroprotective effect of adiponectin on rats with cerebral ischemic-reperfusion injury and explore its possible mechanism.Methods Sixty-four SD rats were divided into normal group (C) and diabetic group (D) randomly.Type 2 diabetic rats model were made by high-fat diet before the middle cerebral artery occulation model (MCAO) surgery.Each group was divided into two subgroups.CAPNand DAPN groups were given exogenous recombinant globular adiponectin via jugular vein one hour after ischemic-reperfusion injury,C0 and D0 groups were given the same amount of normal saline at the same time.Body weight and blood glucose of the rats were measured before ischemia.We also evaluated the neurological function of rats 24 h after treatment according to Longa criteria and observed the morphological changes of cells in brain area via HE staining.The vascular density in ischemic-reperfusion injury area was detected through 3D confocal image system 2 weeks after the treatment.Results The body weight of diabetic rats was significantly lower than normal rats((284.06 ± 19.85)vs (220.31 ±21.87) g,t =8.634,P =0.000).Blood glucose of diabetic rats before ischemia was significantly higher than normal rats ((4.36±0.13)vs(22.92 ± 1.58) mmol/L,t =11.74,P =0.000).Compared with C0 group,the neurological function score of CAPN group was lower(2.29 ± 0.69 vs 17.0 ± 0.69,t =2.186,P =0.038).Compared with D0 group,the neurological function score of DAPN group was lower(2.89 ± 0.33 vs 2.40 ±0.51,t =2.567,P =0.018),too.HE staining showed that the neuronal injury were milder in CAPN,DAPN group,compared with C0,D0 group,respectively.Adiponectin increased the vascular density of ischemic cortex inC group ((2014.58±61.18)/0.002 mm2 vs(3211.95 ±71.64)/0.002 mm2,t =12.16,P=0.023) and D group ((502.86 ± 30.43)/0.002 mm2 vs (1426.69 ± 97.24)/0.002 mm2,t =25.64,P =0.001).Adiponectin increased the vascular density of ischemic striatum in C group (472.59 ± 4.78)/0.002mm2 vs (736.60 ±104.90) /0.002 mm2,t=7.11,P=0.007) and D group (432.04 ±4.65)/0.002 mm2 vs (1780.75 ± 74.54)/0.002 mm2,t =51.08,P =0.000).Conclusions Adiponectin exerts the neuroprotective effect on cerebral ischemic-reperfusion injury in normal and diabetic rats.And it may protect the brain through promoting angiogenesis.