敲除小鼠Ormdl3基因可部分缓解降植烷诱导的狼疮表型  

Ormdl3 Deficiency Partially Alleviates the Development of Clinical Phenotype for the Pristane-induced Lupus Mice

作　　者：贾维 马占兵[1,2] 刘奇迹[3] 党洁[1,2] JIA Wei;MA Zhanbing;LIU Qiji;DANG Jie(School of Basic Medicine,Ningxia Medical University,Yinchuan750004,China;Key laboratory of Fertility Preservation and Maintenance of Ministry of Education,Ningxia Medical University,Key Laboratory of Reproduction and Genetics of Ningxia Hui Autonomous Region,Yinchuan750004,China;Key Laboratory of Experimental Teratology of Ministry of Education,Shandong University,Jinan250001,China)

机构地区：[1]宁夏医科大学基础医学院,银川750004 [2]宁夏医科大学生育力保持教育部重点实验室,宁夏回族自治区生殖与遗传重点实验室,银川750004 [3]山东大学实验畸形学教育部重点实验室,济南250001

出　　处：《宁夏医科大学学报》2020年第1期1-7,共7页Journal of Ningxia Medical University

基　　金：国家自然科学基金(81560273);宁夏自然科学基金(NZ17063)。

摘　　要：目的探讨ORMDL3基因与系统性红斑狼疮(SLE)临床表型之间的关系。方法采用TALEN技术构建Ormdl3基因敲除小鼠。取纯合敲除小鼠(Ormdl3^-/-)与同窝野生小鼠(Ormdl3^+/+)各20只,分为4组,分别腹腔注射降植烷与PBS各0.5 mL,在注射3个月和6个月后比较各组小鼠24 h尿蛋白水平,HE染色比较肾脏损伤程度,称重比较脾脏质量、体质量,流式细胞术比较脾脏组织CD4^+/CD8^+T细胞比例。结果(1)注射降植烷3个月及6个月后,Ormdl3^-/-敲除小鼠脾脏肿大程度低于同时注射降植烷的Ormdl3^+/+野生小鼠;(2)Ormdl3^-/-敲除小鼠在注射降植烷6个月后,24 h尿蛋白水平较同样注射降植烷的Ormdl3^+/+野生小鼠差异无统计学意义(P=0.066);HE染色结果显示Ormdl3^-/-敲除小鼠在注射降植烷后肾脏损伤程度较注射降植烷的Ormdl3^+/+野生小鼠轻。(3)降植烷诱导的Ormdl3^+/+野生小鼠脾脏CD8^+T细胞比例下降(P<0.05),进而导致CD4^+/CD8^+T细胞比例升高(P<0.05),而Ormdl3^-/-敲除小鼠在注射降植烷后能够抵抗CD4^+/CD8^+T细胞比例上升的趋势。结论Ormdl3基因缺失可部分缓解降植烷诱导的狼疮小鼠模型表型程度,初步提示ORMDL3可能在导致SLE发病过程中具有一定作用。Objective To investigate the relationship between ORMDL3 gene and clinical phenotype of systemic lupus erythematosus(SLE).Methods Using TALEN technology,Ormdl3 gene knockout mice were constructed.Twenty homozygous knockout(KO)mice(Ormdl3^-/-)and wild mice(Ormdl3^+/+)were divided into four groups.They were injected intraperitoneally with 0.5 mL of Pristane and 0.5 mL of PBS respectively.After three and six months of injection,the 24 h urine protein level of mice in each group was compared.HE staining was used to compare the degree of kidney injury.Spleen weight and body weight were compared.The proportion of CD4^+/CD8^+T lymphocytes in spleen tissue was compared by flow cytometry.Results(1)After the injection of Pristane,the spleen enlargement of Ormdl3 KO mice was significantly lower than that of wild mice when three or six months later.(2)After 6 months followed by Pristane injection,the 24 h urinary protein level of Ormdl3 KO mice and wild mice were not statistically significant(P=0.066).Compared with Ormdl3 KO mice,the results of HE staining in the kidneys of mice showed more severe degree of renal injury in wild-type mice both after injected Pristane 6 months.(3)The proportion of CD8^+T cells in spleen of wild-type mice induced by Pristane decreased significantly(P<0.05),which led to an obvious increase in the proportion of CD4^+/CD8^+T cells(P<0.05),while the lacking of Ormdl3 could evidently resist the increase of the proportion of CD4^+/CD8^+T cells by injecting Pristane.Conclusion The absence of Ormdl3 partially alleviated the degree of phenotypic of the lupus induced by Pristane in mice,preliminarily suggesting that ORMDL3 may play a role in the pathogenesis of SLE.

关 键 词：血清类黏蛋白样3 系统性红斑狼疮 降植烷诱导狼疮小鼠 

分 类 号：R593.24[医药卫生—内科学]