中国临床药理学杂志2024，Vol.40Issue(13)：1938-1942,5.DOI:10.13699/j.cnki.1001-6821.2024.13.019
基于RIP1/RIP3探究西地那非对勃起功能障碍大鼠睾丸的影响
Exploring the effects of sildenafil on testicular of rats with erectile dysfunction based on RIP1/RIP3
摘要
Abstract
Objective To investigate the role of programmed necrosis pathway in testicular tissue damage in rats with erectile dysfunction(ED)and the mechanism of sildenafil intervention.Methods An ED rat model was established by high-fat chow feeding,and the rats were randomly divided into model group,experimental group,interleukin 18 group,and experimental+interleukin 18 group;10 rats were randomly selected as the normal control group.The experimental group was gavaged with 20 mg·kg-1sildenafil;the interleukin 18 group was injected intraperitoneally with 0.2 μg·kg-1interleukin 18 recombinant protein;the experimental+interleukin 18 group was gavaged with an equal amount of sildenafil,and the experimental+interleukin 18 group was injected intraperitoneally with an equal amount of interleukin 18 recombinant protein;the normal control and model groups were given with an equal amount of 0.9％NaCl by gavage and intraperitoneally injected with an equal amount of saline;and the experimental group was injected with an equal amount of 0.9％NaCl.Interleukin 18 group was gavaged with an equal amount of 0.9％NaCl,and the five groups of rats were administered once a day at regular intervals for 14 consecutive days.Reverse transcription polymerase chain reaction(RT-qPCR)and Western blotting were used to detect the expression of receptor-interacting protein kinase 1(RIP1),receptor-interacting protein kinase 3(RIP3),mixed-spectrum kinase structural domain-like protein(MLKL),and calcium-calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)in rat testis tissues.Results The relative expression levels of RIP1 protein in the normal control group,model group,experimental group,interleukin 18 group and experimental+interleukin 18 group were 0.58±0.05,0.99±0.09,0.71±0.05,1.23±0.07 and 0.81±0.07;the relative expression levels of RIP3 protein were 0.61±0.05,1.05±0.10,0.77±0.04,1.19±0.07 and 0.84±0.08,respectively;the relative expression levels of MLKL protein were 0.63±0.05,1.13±0.08,0.79±0.05,1.30±0.02 and 1.00±0.04,respectively;the relative expression levels of CaMK Ⅱ protein were 0.54±0.04,1.12±0.07,0.77±0.05,1.36±0.04 and 1.00±0.07;the differences of the above indexes were statistically significant when the model group was compared with the normal control group,the experimental group was compared with the model group,the interleukin 18 group was compared with the model group,and the experimental+interleukin 18 group was compared with the interleukin 18 group(all P＜0.05).Conclusion The RIP1/RIP3-mediated necroptosis pathway plays multiple regulatory roles in testicular injury in ED rats,and sildenafil may improve testicular function in rats by inhibiting the above necroptosis signaling pathway.关键词
西地那非/勃起功能障碍/程序性坏死/受体相互作用蛋白激酶1/受体相互作用蛋白激酶3/睾丸Key words
sildenafil/erectile dysfunction/necroptosis/receptor-interacting protein 1/receptor-interacting protein 3/testicular分类
医药卫生引用本文复制引用
刘玉莲,牛立盼,杨培,张蕊,刘凤霞..基于RIP1/RIP3探究西地那非对勃起功能障碍大鼠睾丸的影响[J].中国临床药理学杂志,2024,40(13):1938-1942,5.基金项目
国家自然科学基金资助项目(81860781) （81860781）
新疆维吾尔自治区自然科学基金资助项目(2021D01C280) （2021D01C280）
