CACNA1D基因突变大鼠血压变化及其与血浆Th1、Th2细胞因子的关系  

Changes of blood pressure and their relationships with plasma Th1 and Th2 cytokines in rats with CACNA1D gene mutation

作　　者：吴小盈[1,2] 陈慧[1,2] 林鹏程 王欢[1,2] 毛高伟 WU Xiaoying;CHEN Hui;LIN Pengcheng;WANG Huan;MAO Gaowei(不详;The Second Department of Cardiology,Fujian Provincial Hospital,Fuzhou 350001,China)

机构地区：[1]福建医科大学省立临床医学院,福州350001 [2]福建省立医院心血管内二科

出　　处：《山东医药》2022年第29期6-9,共4页Shandong Medical Journal

基　　金：福建省自然科学基金项目(2018J01240)。

摘　　要：目的观察CACNA1D基因突变大鼠血压变化,并分析其与血浆Th1、Th2细胞因子的关系。方法通过CRISPR/Cas9基因编辑技术创建CACNA1D基因c.920A>G突变SD大鼠并与野生型SD大鼠杂交,对繁殖至F2代的大鼠进行基因型鉴定,抽取野生型(AA型)、杂合突变型(AG型)、纯合突变型(GG型)SD大鼠14、22、12只,均雌雄各半。分别于实验鼠鼠龄第8、9、10、17、21、26、28、32周时采用尾袖法检测大鼠尾动脉收缩压,将32周时收缩压≥140 mmHg的大鼠判定为高血压大鼠,收缩压<140 mmHg的大鼠判定为正常血压大鼠。采用ELISA法检测各基因型大鼠32周龄时血浆Th1、Th2细胞因子白细胞介素2(IL-2)、干扰素γ(IFN-γ)、IL-4、IL-5、IL-6、IL-10。结果AA型、AG型、GG型大鼠收缩压在10周龄前比较无统计学意义;10周龄后,AA型大鼠收缩压较前无明显改变,AG型、GG型大鼠收缩压随周龄增长逐渐升高,至28~32周龄时,AG型、GG型大鼠收缩压均高于AA型大鼠(P均<0.01)。32周龄时,AG型、GG型大鼠收缩压均高于同性别AA型大鼠,AG型、GG型雄性大鼠血浆IFN-γ高于AA型雄性大鼠,AG型雄性大鼠血浆IFN-γ/IL-4高于AA型雄性大鼠(P均<0.05);三种基因型雌性大鼠血浆IL-2、IL-4、IL-5、IL-6、IL-10、IFN-γ和IFN-γ/IL-4比较均无统计学差异。32周龄时,共有高血压大鼠17例、正常血压大鼠31例;高血压大鼠血浆IL-4低于正常血压大鼠,IFN-γ/IL-4高于正常血压大鼠(P均<0.05);高血压与正常血压大鼠血浆IL-2、IL-5、IL-6、IL-10、IFN-γ比较差异无统计学意义。结论CACNA1D基因c.920A>G突变大鼠血压高于野生型大鼠,其高血压的发生可能与Th1/Th2细胞功能失衡有关。Objective To observe the blood pressure changes in CACNA1D mutant rats and to analyze their relation-ships with plasma Th1 and Th2 cytokines expression levels.Methods The rats with CACNA1D c.920A>G mutant were constructed using CRISPR/Cas9 technology,and hybridized with wild type SD rats.Rats bred to the F2 generation were genotyped;wildtype rats(AA,n=14),heterozygous rats(AG,n=22)and homozygous rats(GG,n=12)were selected,all sex in half.Systolic blood pressure(SBP)was measured by tail cuff method at the age of 8,9,10,17,21,26,28 and 32 weeks.The rats with SBP≥140 mmHg at 32 weeks were classified as hypertensive rats,and the rats with SBP<140 mmHg were classified as normotensive rats.The plasma levels of Th1 and Th2 cytokines including interleukin-2(IL-2),interferon-γ(IFN-γ),IL-4,IL-5,IL-6 and IL-10 were detected by ELISA.Results There was no significant difference in SBP between AA,AG and GG rats before 10 weeks of age.After 10 weeks of age,the SBP of AA rats did not change sig-nificantly,while the SBP of AG and GG rats gradually increased with age.At the age of 28-32 weeks,the SBP of AG and GG rats were higher than that of AA rats(P<0.01).At 32 weeks,the SBP of AG and GG rats was higher than that of AA rats of the same sex.In male rats,compared with AA rats,plasma IFN-γwas higher in AG and GG rats(all P<0.01),and IFN-γ/IL-4 ratio was higher in AG genotype(P<0.05).In female rats,there were no significant differences in plasma IL-2,IL-4,IL-5,IL-6,IL-10,IFN-γor IFN-γ/IL-4 ratio between AA,AG and GG rats.At the age of 32 weeks,there were 17 hypertensive rats and 31 normotensive rats.Plasma IL-4 was lower while IFN-γ/IL-4 ratio was higher in hyperten-sive rats than in normotensive rats(all P<0.05).There were no significant differences in plasma IL-2,IL-5,IL-6,IL-10 or IFN-γbetween hypertensive and normotensive rats.Conclusion The SBP was higher in CACNA1D gene c.920A>G mutant rats than in wildtype rats.Th1/Th2 cell function imbalance might be correlated with the pathogenesis of hyperten-sion in CACNA1D gen

关 键 词：CACNA1D基因 基因突变 高血压 TH1/TH2失衡 白细胞介素 干扰素 

分 类 号：R541.3[医药卫生—心血管疾病]