中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2012年
8期
709-714
,共6页
苟文军%欧阳科%吕红彬%李青兰%周琦%张俊
茍文軍%歐暘科%呂紅彬%李青蘭%週琦%張俊
구문군%구양과%려홍빈%리청란%주기%장준
过氧化物酶体增生物激活受体-γ激动剂%糖尿病视网膜病变%视网膜神经节细胞%核因子-κB%凋亡
過氧化物酶體增生物激活受體-γ激動劑%糖尿病視網膜病變%視網膜神經節細胞%覈因子-κB%凋亡
과양화물매체증생물격활수체-γ격동제%당뇨병시망막병변%시망막신경절세포%핵인자-κB%조망
Peroxisome proliferator-activated receptor-gamma excitomotor%Diabetic retinopathy%Retinal ganglion cell%Nuclear factor-κB%Apoptosis
背景 糖尿病视网膜病变(DR)作为糖尿病最常见的眼部微血管并发症,已成为人类最重要的致盲性眼病之一.核因子-κB(NF-κB)可通过激活一系列的炎性因子,参与DR的发生与发展. 目的 观察过氧化物酶体增生物激活受体-γ(PPAR-γ)激动剂罗格列酮对链脲佐菌素(STZ)诱导的早期糖尿病大鼠视网膜中NF-κB的表达及其对视网膜神经节细胞(RGCs)凋亡的影响.方法 选择90只健康雄性SPF级Wistar大鼠,应用随机数字表法随机将大鼠分为3个组:正常对照组、糖尿病对照组和罗格列酮治疗组,其中糖尿病对照组和罗格列酮治疗组均采用一次性腹腔注射50 mg/kg STZ的方法建立糖尿病大鼠模型.自糖尿病模型成模后第3天起,罗格列酮治疗组大鼠每日给予罗格列酮3 mg/kg灌胃,正常对照组和糖尿病对照组每日给予等体积的生理盐水灌胃.3个组分别于给药后4、8、12周各取10只大鼠处死,处死前检测各组大鼠的血糖,然后摘除眼球制作眼杯标本,并进行常规组织病理学检查,采用免疫组织化学法检测视网膜中NF-κB p65蛋白的表达,采用TUNEL法测定RGCs的凋亡指数(AI).结果 给药后4、8、12周,糖尿病对照组和罗格列酮治疗组大鼠血糖水平均明显高于正常对照组,差异均有统计学意义(P＜0.01),罗格列酮治疗组与糖尿病对照组大鼠血糖相比,差异均无统计学意义(q=0.81、0.82、1.23,P＞0.05).正常对照组大鼠视网膜结构完整、排列规则,糖尿病对照组大鼠视网膜细胞水肿,排列紊乱,但罗格列酮治疗组大鼠视网膜结构接近正常.正常对照组大鼠视网膜中NF-κB p65呈弱表达,糖尿病对照组和罗格列酮治疗组大鼠视网膜NF-κB p65蛋白的表达(A值)均较正常对照组明显增加,差异均有统计学意义(P＜0.01);给药后8周和12周时,罗格列酮治疗组大鼠视网膜NF-κB p65的表达均较糖尿病对照组明显降低,差异均有统计学意义(q=17.77、15.30,P＜0.01).正常对照组大鼠RGCs层仅见少量凋亡细胞,罗格列酮治疗组大鼠RGCs的AI较糖尿病对照组明显降低,差异均有统计学意义( q=19.28、27.39、49.92,P＜0.01),糖尿病对照组和罗格列酮治疗组大鼠RGCs的AI均明显高于正常对照组(P＜0.01).结论 外源性PPAR-γ激动剂罗格列酮可能通过下调NF-κB的表达抑制糖尿病大鼠RGCs的凋亡,对早期糖尿病大鼠的视网膜具有保护作用.
揹景 糖尿病視網膜病變(DR)作為糖尿病最常見的眼部微血管併髮癥,已成為人類最重要的緻盲性眼病之一.覈因子-κB(NF-κB)可通過激活一繫列的炎性因子,參與DR的髮生與髮展. 目的 觀察過氧化物酶體增生物激活受體-γ(PPAR-γ)激動劑囉格列酮對鏈脲佐菌素(STZ)誘導的早期糖尿病大鼠視網膜中NF-κB的錶達及其對視網膜神經節細胞(RGCs)凋亡的影響.方法 選擇90隻健康雄性SPF級Wistar大鼠,應用隨機數字錶法隨機將大鼠分為3箇組:正常對照組、糖尿病對照組和囉格列酮治療組,其中糖尿病對照組和囉格列酮治療組均採用一次性腹腔註射50 mg/kg STZ的方法建立糖尿病大鼠模型.自糖尿病模型成模後第3天起,囉格列酮治療組大鼠每日給予囉格列酮3 mg/kg灌胃,正常對照組和糖尿病對照組每日給予等體積的生理鹽水灌胃.3箇組分彆于給藥後4、8、12週各取10隻大鼠處死,處死前檢測各組大鼠的血糖,然後摘除眼毬製作眼杯標本,併進行常規組織病理學檢查,採用免疫組織化學法檢測視網膜中NF-κB p65蛋白的錶達,採用TUNEL法測定RGCs的凋亡指數(AI).結果 給藥後4、8、12週,糖尿病對照組和囉格列酮治療組大鼠血糖水平均明顯高于正常對照組,差異均有統計學意義(P＜0.01),囉格列酮治療組與糖尿病對照組大鼠血糖相比,差異均無統計學意義(q=0.81、0.82、1.23,P＞0.05).正常對照組大鼠視網膜結構完整、排列規則,糖尿病對照組大鼠視網膜細胞水腫,排列紊亂,但囉格列酮治療組大鼠視網膜結構接近正常.正常對照組大鼠視網膜中NF-κB p65呈弱錶達,糖尿病對照組和囉格列酮治療組大鼠視網膜NF-κB p65蛋白的錶達(A值)均較正常對照組明顯增加,差異均有統計學意義(P＜0.01);給藥後8週和12週時,囉格列酮治療組大鼠視網膜NF-κB p65的錶達均較糖尿病對照組明顯降低,差異均有統計學意義(q=17.77、15.30,P＜0.01).正常對照組大鼠RGCs層僅見少量凋亡細胞,囉格列酮治療組大鼠RGCs的AI較糖尿病對照組明顯降低,差異均有統計學意義( q=19.28、27.39、49.92,P＜0.01),糖尿病對照組和囉格列酮治療組大鼠RGCs的AI均明顯高于正常對照組(P＜0.01).結論 外源性PPAR-γ激動劑囉格列酮可能通過下調NF-κB的錶達抑製糖尿病大鼠RGCs的凋亡,對早期糖尿病大鼠的視網膜具有保護作用.
배경 당뇨병시망막병변(DR)작위당뇨병최상견적안부미혈관병발증,이성위인류최중요적치맹성안병지일.핵인자-κB(NF-κB)가통과격활일계렬적염성인자,삼여DR적발생여발전. 목적 관찰과양화물매체증생물격활수체-γ(PPAR-γ)격동제라격렬동대련뇨좌균소(STZ)유도적조기당뇨병대서시망막중NF-κB적표체급기대시망막신경절세포(RGCs)조망적영향.방법 선택90지건강웅성SPF급Wistar대서,응용수궤수자표법수궤장대서분위3개조:정상대조조、당뇨병대조조화라격렬동치료조,기중당뇨병대조조화라격렬동치료조균채용일차성복강주사50 mg/kg STZ적방법건립당뇨병대서모형.자당뇨병모형성모후제3천기,라격렬동치료조대서매일급여라격렬동3 mg/kg관위,정상대조조화당뇨병대조조매일급여등체적적생리염수관위.3개조분별우급약후4、8、12주각취10지대서처사,처사전검측각조대서적혈당,연후적제안구제작안배표본,병진행상규조직병이학검사,채용면역조직화학법검측시망막중NF-κB p65단백적표체,채용TUNEL법측정RGCs적조망지수(AI).결과 급약후4、8、12주,당뇨병대조조화라격렬동치료조대서혈당수평균명현고우정상대조조,차이균유통계학의의(P＜0.01),라격렬동치료조여당뇨병대조조대서혈당상비,차이균무통계학의의(q=0.81、0.82、1.23,P＞0.05).정상대조조대서시망막결구완정、배렬규칙,당뇨병대조조대서시망막세포수종,배렬문란,단라격렬동치료조대서시망막결구접근정상.정상대조조대서시망막중NF-κB p65정약표체,당뇨병대조조화라격렬동치료조대서시망막NF-κB p65단백적표체(A치)균교정상대조조명현증가,차이균유통계학의의(P＜0.01);급약후8주화12주시,라격렬동치료조대서시망막NF-κB p65적표체균교당뇨병대조조명현강저,차이균유통계학의의(q=17.77、15.30,P＜0.01).정상대조조대서RGCs층부견소량조망세포,라격렬동치료조대서RGCs적AI교당뇨병대조조명현강저,차이균유통계학의의( q=19.28、27.39、49.92,P＜0.01),당뇨병대조조화라격렬동치료조대서RGCs적AI균명현고우정상대조조(P＜0.01).결론 외원성PPAR-γ격동제라격렬동가능통과하조NF-κB적표체억제당뇨병대서RGCs적조망,대조기당뇨병대서적시망막구유보호작용.
Background As one of the most common microvascular complication of diabetes in eyes,diabetic retinopathy (DR) is one of the most important cause of blindness.Nuclear factor-kappa B (NF-κB) is involved in the occurrence and development of the disease through the activation of a series of inflammatory cytokines.Objective The present study was to investigate the effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) excitomotor,rosiglitazone,on NF-κB expression and apoptosis of the retinal ganglion cells (RGCs) in the retina with diabetes mellitus. Methods Ninety SPF male Wistar rats were randomized into normal control group,diabetic control group and rosiglitazone group.Diabetes mellitus was induced by intraperitoneal injection of 50 mg/kg streptozotocin(STZ).Then 3 mg/kg rosiglitazone was intragastricly administered once per day in the rosiglitazonegroup,and the same volume of saline solution was used at the same way in the normal control group and diabetic control group from 3 days after modeling.The rats were sacrificed and the eye cups specimen was made at 4,8 and 12 weeks after usage of drugs.Retinal histopathological examination was performed by hematine-eosin staining,and expression of NF-κB p65 protein in retina and apoptotic index(AI) of RGCs were detected by immunohistochemistry and TUNEL assay,respectively in different time points mentioned above.The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State and Technology Commission.Results The blood glucose level was significantly elevated at various time points in the diabetic control group and rosiglitazone group compared with normal control group (P＜0.01 ),and that of the rosiglitazone group was significantly declined in comparison to the diabetic control group (q =0.81,0.82,1.23,P＞ 0.05 ).Normal retinal structure was seen in the normal control group,and edema retinal cell and disorder of retinal layers were exhibited in the diabetic control group.Retinal structure was almost normal in the rosiglitazone group.The NF-κB p65 was expressed weakly in the retina of normal control group,but the expression of NF-κB p65 was significantly elevated in the diabetic control group and rosiglitazone group compared with the normal control group(P＜0.01 ).However,the expression of NF-κB p65(A value)was significantly decreased in the rosiglitazone group compared with diabetic control group at 8 weeks and 12 weeks( q=17.77,15.30,P＜0.01 ).There were a few apoptotic cells in rat retina of the normal control group.Compared with the normal control group,the AI of the diabetic control group and rosiglitazone group was significantly reduced(P＜0.01 ).However,the AI of RGCs in the rosiglitazone group was significantly lower than that of diabetic control group in various time points (q =19.28,27.39,49.92,P＜0.01 ). Conclusions As one of the PPAR-γexcitomotors,rosiglitazone can inhibit apoptosis of RGCs through downregulating the expression of NF-κB in rat retina with diabetes mellitus,indicating a protective effect of rosiglitazone on retina in diabetic rat.
