Tanshinone IIA contributes to the pathogenesis of endometriosis via renin angiotensin system by regulating the dorsal root ganglion axon sprouting
Tanshinone IIA contributes to the pathogenesis of endometriosis via renin angiotensin system by regulating the dorsal root ganglion axon sprouting
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DOI：
10.1016/j.lfs.2019.117085
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发表时间：
2020-01-01
期刊：
影响因子：
6.1
通讯作者：
Gong, Xin
中科院分区：
文献类型：
--
作者：
Chen, Zhen-zhen;Gong, Xin
目的：本研究旨在探讨丹参酮IIA对子宫内膜异位症（EMs）所致疼痛综合征的缓解作用及其机制。将大鼠随机分为假手术组、模型组、阳性对照组、丹参酮IIA（L）组（3 mg/kg/d）和丹参酮IIA（H）组（12 mg/kg/d）。连续给药21天后测量异位内膜的体积。采用酶联免疫吸附法（ELISA）检测血清雌二醇（E2）水平。采用免疫组化和Western Blotting方法检测背根神经节（DRG）神经元血管紧张素原（AGT）、肾素（REN）、血管紧张素转换酶（ACE）、血管紧张素II（ANGII）和血管紧张素II 2型受体（AT 2）的蛋白表达。实时定量PCR检测AGT和ANGII mRNA的表达水平。结果：丹参酮IIA能显著抑制异位内膜的生长。丹参酮IIA能提高EMs大鼠的缩足阈，从而减轻EMs大鼠的机械性痛敏。丹参酮IIA通过降低DRG神经元AGT、REN、ACE、ANGII和AT 2的蛋白表达，调节DRG的肾素血管紧张素系统（RAS）。结论：丹参酮IIA可能通过抑制E2、ANGII和AT 2的表达，从而抑制DRG发芽，提高痛敏阈值，从而抑制EMs大鼠的痛反应。
Aims: Our study was designed to explore the function and mechanism of Tanshinone IIA in alleviating pain syndrome caused by endometriosis (EMs).Main methods: Female Sprague-Dawley rats went through autotransplantation operation to establish EMs model. The rats were randomly divided into five groups: sham, model, positive, Tanshinone IIA (L) (3 mg/kg/d) and Tanshinone IIA (H) (12 mg/kg/d) group. Volume of ectopic endometrium was measured after 21 days of continuous administration. Serum estradiol (E2) was detected by enzyme linked immunosorbent assay (Elisa). The protein expression of angiotensinogen (AGT), renin (REN), angiotensin converting enzyme (ACE), angiotensin II (ANGII) and angiotensin II type 2 receptor (AT2) in the dorsal root ganglion (DRG) neurons were measured by immunohistochemistry and Western Blotting. The mRNA expression levels of AGT and ANGII were measured by Real-time polymerase chain reaction (PCR).Key findings: Tissue measurements showed that tanshinone IIA significantly inhibited the growth of ectopic endometrium. Tanshinone IIA could improve the paw withdrawal threshold thus reducing the mechanical hyperalgesia of EMs rats. Moreover, Tanshinone IIA regulated the DRG renin angiotensin system (RAS) by reducing the protein expression of AGT, REN, ACE, ANGII and AT2 in DRG neurons. Furthermore, Real-time PCR results also showed that the mRNA expression levels of AGT and ANGII in the DRG neurons were decreased.Significance: The Tanshinone IIA inhibitory effect on the EMs associated pain in EMs rats might occur through decreasing the expression of E2, ANGII and AT2, thus halting DRG sprouting and promoting hyperalgesia threshold.