中国全科医学2017，Vol.20Issue(12)：1474-1479,6.DOI:10.3969/j.issn.1007-9572.2017.12.013
蛋白质精氨酸甲基转移酶1-非对称性二甲基精氨酸-二甲基精氨酸二甲胺水解酶1路径在肝纤维化、肾小管间质纤维化大鼠组织中的作用及意义
Role and Significance of PRMT1 - ADMA - DDAH1 Pathway in Rats with Hepatic and Renal Tubulointerstitial Fibrosis
摘要
Abstract
Objective To study the changes of protein - arginine N - methyltransferases 1 (PRMT1) - asymmetrical dimethylarginine (ADMA) - dimethylarginine dimethylaminohydrolase 1 (DDAH1)axis in rat models of hepatic and renal tubulointerstitial fibrosis,and discuss the correlation between serum ADMA levels and degree of fibrosis. Methods From September to December 2015,20 Sprague - Dawley rats were randomly selected from 40 male SPF Sprague - Dawley rats,and equally divided into control group of solvent (group A)and model group of hepatic fibrosis (group B);the remaining 20 Sprague - Dawley rats were randomly divided into sham operation group (group C)and model group (group D),each had 10 rats. The rat models of hepatic fibrosis (group B)and tubulointerstitial fibrosis (group D)were established by chronic exposure to carbon tetrachloride (CCl 4 )and unilateral ureteral obstruction. The solvent control model (group A)and sham operation model (group C)were established by subcutaneous injection of the same amount of peanut oil and unilateral ureteral separation without ligation respectively. After 8 - week and 2 - week intervention for rats in group A and B,group C and D respectively, Masson trichrome staining method was calculated percentages of areas of hepatic and renal collagen fibers;the levels of hydroxyproline (Hyp)in hepatic and renal were detected by chemical colorimetry. Serum ADMA levels were measured by the modified HPLC method. The expression levels of PRMT1 and DDAH1 in hepatic and renal tissues were detected by Western blotting. Results The serum ADMA levels of group A,group B,group C and group D were (0. 43 ± 0. 07) (1. 10 ± 0. 21) (0. 45 ± 0. 03) (1. 26 ± 0. 21)μmol/ L respectively. The serum ADMA level of group B was higher than that of group A (t= 6. 32,P < 0. 05). The serum ADMA level of group D was higher than that of group C (t = 6. 96,P < 0. 05). There was a positive correlation between the ADMA level in serum and the percentage of areas of hepatic and renal collagen fibers (r = 0. 913, 0. 934 respectively,P < 0. 05). There was a positive correlation between the ADMA level in serum and the level of Hyp in hepatic and renal tissues (r = 0. 856,0. 878 respectively,P < 0. 05). The expression level of PRMT1 in hepatic tissues of group B was higher than that of group A,while its expression level of DDAH1 was lower than that of group A (P < 0. 05). The expression level of PRMT1 in renal tissues of group D was higher than that of group C,while its expression level of DDAH1 was lower than that of group C (P < 0. 05). Conclusion Under the condition of hepatic and renal fibrosis,increased expression of PRMT1 and decreased expression of DDAH1 in PRMT1 - ADMA - DDAH1 can lead to elevated levels of serum ADMA,cause damages of capillary endothelial cells around hepatic sinusoids and renal tubules,and thus involve in the initiation of and pathological changes of the fibrosis process.关键词
纤维化/模型,动物/蛋白质精氨酸N-甲基转移酶/非对称性二甲基精氨酸Key words
Fibrosis/Models/animal/Protein - arginine N - methyltransferases/Asymmetrical dimethylarginine分类
医药卫生引用本文复制引用
马雪丰,张景耀,毛庆,陈果,秦德萍,李傲..蛋白质精氨酸甲基转移酶1-非对称性二甲基精氨酸-二甲基精氨酸二甲胺水解酶1路径在肝纤维化、肾小管间质纤维化大鼠组织中的作用及意义[J].中国全科医学,2017,20(12):1474-1479,6.基金项目
国家自然科学基金资助项目(81001675) （81001675）
重庆市科委前沿与应用基础研究(一般)项目(cstc2014jcyjA10030) （一般）
