恩格列净对2型糖尿病小鼠脾脏髓源性抑制细胞增殖的影响  

Effect of empagliflozin on proliferation of splenic MDSC in type 2 diabetes mice

作　　者：谢修竹 张金英[1] 张琳[1] 靳丽媛 叶平[1] Xie Xiuzhu;Zhang Jinying;Zhang Lin;Jin Liyuan;Ye Ping(Chinese PLA Medical School/Department of Cardiology,Second Medical Center,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]解放军总医院研究生院、解放军总医院第二医学中心心血管内科,北京100853

出　　处：《中华老年心脑血管病杂志》2023年第6期625-628,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81900730)。

摘　　要：目的探讨恩格列净对2型糖尿病小鼠脾脏髓源性抑制细胞(MDSC)增殖的影响。方法选择C57BL/6J小鼠5只作为对照组。KKay自发2型糖尿病小鼠10只,采用高脂KK鼠料诱导2周,2型糖尿病模型建立后随机分入模型组4只和治疗组6只;对照组和模型组小鼠给予普通饮水,治疗组给予恩格列净3.75 mg/(kg·d)灌胃。各组小鼠继续饲养12周,监测随机血糖和体质量。12周后麻醉下留取血液用于后续血清炎性因子白细胞介素(IL)-6、IL-10和TNF-α检测,测量脾脏长度,称重后计算脾脏指数。采用苏木精-伊红染色,流式细胞术检测各组小鼠脾脏MDSC水平。结果与对照组比较,模型组小鼠血清IL-6、TNF-α水平明显升高,IL-10水平明显降低,治疗组小鼠血清IL-6水平明显升高,差异有统计学意义(P<0.05,P<0.01)。与模型组比较,治疗组小鼠血清IL-6、TNF-α水平明显降低,IL-10水平明显升高,差异有统计学意义(P<0.05,P<0.01)。模型组和治疗组脾脏MDSC水平明显高于对照组[(2.90±0.92)%、(4.47±1.00)%vs(1.19±0.41)%,P<0.01],且治疗组MDSC水平较模型组明显升高,差异有统计学意义(P<0.05)。结论恩格列净能够改善血清炎性因子水平和脾脏免疫环境,促进脾脏MDSC增殖,从而改善全身炎症状态。Objective To investigate the effect of empagliflozin on the proliferation of splenic myeloid-derived suppressor cells(MDSC)in type 2 diabetes mellitus(T2DM)mice.Methods Five C57BL/6J mice were used as control group.Ten KKay spontaneous diabetes mice were induced with high-fat KK mouse diet for 2 weeks.After the establishment of T2DM model,they were randomly divided into model group(4 mice)and treatment group(6 mice).The mice in the control and model groups were given regular water,while the treatment group was given 3.75 mg/(kg·d)empagliflozin by gavage.Their blood glucose and body weight were monitored during the 12 weeks'feeding.In the end of feeding,their blood samples were collected for detection of serum inflammatory cytokines IL-6,IL-10 and TNF-α,and the spleen of each mouse was removed,measured for length and weighed to calculate spleen index.HE staining was used to observe the morphological changes of the half of spleen from each mouse,and flow cytometry was employed to determine the percentage of MDSC in the other half of spleen.Results Compared with the con-trol group,the serum levels of IL-6 and TNF-α were significantly increased,while that of IL-10 was obviously decreased in the model group(P<0.05,P<0.01).The empagliflozin group had higher IL-6 level than the control group(P<0.05,P<0.01),and lower IL-6 and TNF-α levels and higher IL-10 level when compared with the model group(P<0.05,P<0.01).Flow cyto-metry showed the percentage of MDSC was obviously higher in the model group and the treatment group than the control group[(2.90±0.92)%and(4.47±1.00)%vs(1.19±0.41)%,P<0.01],and was significantly increased in the treatment group than the model group(P<0.05).Conclusion Empagliflozin reduces serum inflammatory factor levels,improves the im-mune environment of the spleen,and promotes the proliferation of splenic MDSC,and thus improves the systemic inflammatory state.

关 键 词：降血糖药 髓源性抑制细胞 小鼠 糖尿病 2型 

分 类 号：R587.1[医药卫生—内分泌]