CAJ | 학술논문

目的：观察通心络胶囊对糖尿病视网膜病变（ DR） KK/Upj-Ay小鼠血液及视网膜炎性因子表达的影响。方法选取自发性2型糖尿病KK/Upj-Ay小鼠40只（12周龄，雄性）和C57BL/6小鼠10只（12周龄，雄性，对照组）。将KK/Upj-Ay小鼠按空腹血糖（ FBG）由低到高排列后，再根据随机数字表法分为模型组、通心络低剂组、通心络中剂组和通心络高剂组（各10只），后3组分别给予小鼠1、2、4 g生药/kg的通心络胶囊。对照组和模型组小鼠灌胃等体积的蒸馏水。均1次/d，灌胃12周。给药后12周，测定小鼠血-视网膜屏障功能；流式细胞仪测定小鼠血液中炎性细胞因子〔肿瘤坏死因子α（ TNF-α）、细胞间黏附分子1（ ICAM-1）、白介素6（ IL-6）、白介素1β（ IL-1β）〕水平；Real-time PCR和蛋白质印迹法分别测定小鼠视网膜炎性因子mRNA及蛋白表达水平。结果给药后12周，模型组小鼠视网膜依文思蓝（ EB）含量高于对照组，血液中TNF-α、ICAM-1、IL-6、IL-1β水平高于对照组，视网膜TNF-α、ICAM-1、IL-6、IL-1β mRNA及蛋白表达水平高于对照组（ P<0.05）；通心络中、高剂组小鼠视网膜EB含量低于模型组（P<0.01）；通心络中、高剂组小鼠血液中TNF-α、ICAM-1、IL-1β水平低于模型组，通心络各剂量组小鼠血液 IL -6水平低于模型组（ P <0.05）；通心络各剂量组小鼠视网膜 TNF -α、ICAM-1、IL-6、IL-1β mRNA及蛋白表达水平低于模型组（ P<0.01）。结论通心络胶囊能改善KK/Upj-Ay小鼠血-视网膜屏障功能，抑制其全身炎性因子及视网膜局部炎性因子表达，从而改善KK/Upj-Ay小鼠DR。
목적：관찰통심락효낭대당뇨병시망막병변（ DR） KK/Upj-Ay소서혈액급시망막염성인자표체적영향。방법선취자발성2형당뇨병KK/Upj-Ay소서40지（12주령，웅성）화C57BL/6소서10지（12주령，웅성，대조조）。장KK/Upj-Ay소서안공복혈당（ FBG）유저도고배렬후，재근거수궤수자표법분위모형조、통심락저제조、통심락중제조화통심락고제조（각10지），후3조분별급여소서1、2、4 g생약/kg적통심락효낭。대조조화모형조소서관위등체적적증류수。균1차/d，관위12주。급약후12주，측정소서혈-시망막병장공능；류식세포의측정소서혈액중염성세포인자〔종류배사인자α（ TNF-α）、세포간점부분자1（ ICAM-1）、백개소6（ IL-6）、백개소1β（ IL-1β）〕수평；Real-time PCR화단백질인적법분별측정소서시망막염성인자mRNA급단백표체수평。결과급약후12주，모형조소서시망막의문사람（ EB）함량고우대조조，혈액중TNF-α、ICAM-1、IL-6、IL-1β수평고우대조조，시망막TNF-α、ICAM-1、IL-6、IL-1β mRNA급단백표체수평고우대조조（ P<0.05）；통심락중、고제조소서시망막EB함량저우모형조（P<0.01）；통심락중、고제조소서혈액중TNF-α、ICAM-1、IL-1β수평저우모형조，통심락각제량조소서혈액 IL -6수평저우모형조（ P <0.05）；통심락각제량조소서시망막 TNF -α、ICAM-1、IL-6、IL-1β mRNA급단백표체수평저우모형조（ P<0.01）。결론통심락효낭능개선KK/Upj-Ay소서혈-시망막병장공능，억제기전신염성인자급시망막국부염성인자표체，종이개선KK/Upj-Ay소서DR。
Objective ToinvestigatetheeffectofTongxinluocapsuleoninflammatorycytokinesexpressionofblood andretinainKK/Upj-Aymicewithdiabeticretinopathy(DR).Methods 40spontaneoustype2diabeticKK/Upj-Aymice (12 weeks of age,male)and 10 C57BL/6 mice(12 weeks of age,male)were selected as study subjects. According to fasting blood-glucose( FBG)level and random number table,KK/Upj-Ay mice were divided into model group,Tongxinluo low dose group(1 g/kg),Tongxinluo middle dose group(2 g/kg)and Tongxinluo high dose group(4 g/kg),10 mice in each group. Mice in Tongxinluo group were given Tongxinluo capsule intragastrically,once a day,for 12 weeks. The same volume of distilled water was given to the mice in control group and model group,once a day,for 12 weeks. 12 weeks after treatment,the function of blood retinal barrier was determined. Blood levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α),intercellular adhesion molecule 1(ICAM-1),interleukin 6(IL-6)and interleukin 1 beta(IL-1β)were de-termined by FCM. The mRNA and protein expression levels of inflammatory cytokines in retina were determined by real-time PCR andWesternblotting,respectively.Results 12weeksaftertreatment,retinaevansblue(EB)contentofmiceinmodelgroup were significantly higher than that in control group(P<0. 05). Blood levels of TNF-α,ICAM-1,IL-6 and IL-1β of mice in model group were significantly higher than those in control group(P<0. 05). The retina mRNA and protein expression levels of TNF-α,ICAM-1,IL-6 and IL-1β of mice in model group were higher than those in control group(P<0. 05).The retina EB content of mice in Tongxinluo middle dose group and Tongxinluo high dose group were significantly lower than that in model group,respectively(P<0. 01). Blood levels of TNF-α,IL-1β and ICAM-1 of mice in Tongxinluo middle dose group and Tongxinluo high dose group were significantly lower than those in model group,respectively(P<0. 05). Blood IL-6 levels of mice in Tongxinluo low,middle,high dose groups were significantly lower than that in model group,respectively( P<0. 05). The retina mRNA and protein expression levels of TNF-α,ICAM-1,IL-6 and IL-1β of mice in Tongxinluo low, middleandhighdosegroupsweresignificantlylowerthanthoseinmodelgroup(P<0.01).℅onclusion Tongxinluocapsule can improve blood retinal barrier function of KK/Upj-Ay mice,and inhibit the inflammatory cytokines expression of whole body and retina.