|
|
|
| Based on estrogen receptor-mediated neurotrophic factor pathway to explore the protective effect of Zuogui Pills on cerebral ischemia-reperfusion injury |
| LIU Hong1,2 YI Yajing3 YU Ying3 DAI Qiaomei1 ZHANG Yuwei1 YANG Jing1 ZHANG Bo4 ZHONG Lili5 |
1.School of Basic Medical College, Heilongjiang University of Traditional Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
2.Postdoctoral Mobile Station, Heilongjiang University of Traditional Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
3.Graduate School, Heilongjiang University of Traditional Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
4.Chinese Medicine Research Institute, Heilongjiang University of Traditional Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
5.the First Affiliated Hospital, Heilongjiang University of Traditional Chinese Medicine, Heilongjiang Province, Harbin 150040, China |
|
|
|
Abstract Objective To explore whether Zuogui Pills can play a neuroprotective role by regulating estrogen receptor pathway. Methods A total of 108 female SD rats were eight-ten weeks old and SPF grade level. They were randomly divided into six groups: sham operation group (incision without thread insertion), I/R group (middle cerebral artery occlusion [MCAO] operation by longa thread bolt method), OVX+I/R group (ovariectomy+MCAO operation), OVX+I/R+Zuogui Pills group (ovariectomy+MCAO operation+Zuogui Pills 1.62 g/kg gavage), OVX+I/R+Zuogui Pills+ICI182780 group (ovariectomy+MCAO operation+Zuogui pills gavage+ICI182780 3 mg/kg intraperitoneal injection), OVX+I/R +17β-estradiol group (ovariectomy+MCAO+17β-estradiol 100 μg/kg intraperitoneal injection), 18 rats in each group. The neurological deficit score was used to evaluated the sensory motor function of rats of each group, the novel object recognition experiment was used to observe the memory of rats, and the protein and mRNA expressions of estrogen receptor (ER) α, ERβ, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), tyrosine kinase (Trk) A, TrkB, phosphorylated cAMP response element binding (p-CREB) and CREB were observed. Results The motor function and memory of the rats in the I/R group were lower than those in the sham operation group (P ＜ 0.05); the motor function and memory of the rats in the OVX+I/R group were lower than those in the I/R group (P ＜ 0.05); the motor function and memory of rats in the OVX+I/R+Zuogui Pills group were higher than those of the OVX+I/R group (P ＜ 0.05); the motor function and memory of the OVX+I/R+Zuogui Pills+ICI182780 group were lower than that of OVX+I/R+ Zuogui Pills group (P ＜ 0.05); OVX+I/R+Zuogui Pills group motor function and memory compared with OVX+I/R+17β-estradiol group, and the differences were not statistically significant (P ＞ 0.05). The protein and mRNA (except BDNF) expressions of ERα, ERβ, BDNF, NGF, TrkA, TrkB, and P-CREB in the I/R group were higher than those in the sham operation group (P ＜ 0.05 or P ＜ 0.01); the expression of above indexes in the OVX+I/R group were lower than that in the I/R group (P ＜ 0.05 or P ＜ 0.01); the expression of above indexes in the OVX+I/R+Zuogui Pills group were higher than that in the OVX+I/R group; the expression of above indexes in the OVX+I/R+Zuogui Pills+ICI182780 group were lower than that in the OVX+I/R+Zuogui Pills group (P ＜ 0.05 or P ＜ 0.01). Compared with the OVX+I/R+17β-estradiol group, the expression of each indexes in the OVX+I/R+Zuogui Pills group were not statistically differences (P ＞ 0.05). Conclusion Zuogui Pills may improve the brain I/R damage of OVX rats through ER-mediated BDNF-TrkB and NGF-TrkA signal transduction.
|
|
|
|
|
|
[1] Liang CC，Shaw SWS，Huang YH，et al. Bladder transplantation of amniotic fluid stem cell may ameliorate bladder dysfunction after focal cerebral ischemia in rat [J]. Stem Cells Transl Med，2017，6（4）：1227-1236.
[2] Zhang B，Subramanian S，Dziennis S，et al. Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke[J]. J Immunol，2010，184（8）：4087-4094.
[3] Jia J，Guan D，Zhu W，et al. Estrogen inhibits Fas-mediated apoptosis in experimental stroke [J]. Exp Neurol，2009， 215（1）：48-52.
[4] Wassertheil-Smoller S，Hendrix S，Limacher M，et al. Effect of estrogen plus progestin on stroke in postmenopausal women：the Women’s Health Initiative：a randomized trial [J]. JAMA，2003，289（20）：2673-2684.
[5] 姚蕾，刘春慧，卓拉.左归丸组方分析及实验研究进展[J].亚太传统医药，2019，15（8）：214-216.
[6] 陈武杰，陈秀玲，孙韶刚，等.左归丸治疗肝肾阴虚型脑梗死恢复期50例临床观察[J].新中医，2010，42（8）：14-15.
[7] 银忠甫.天麻钩藤饮合左归丸化裁治疗眩晕疗效观察[J].四川中医，2012，30（1）：63.
[8] 李妍.中医“肾主生殖”理论探讨及现代研究[D].哈尔滨：黑龙江中医药大学，2007.
[9] 王文健，沈自尹，张新民，等.补肾法对老年男性下丘脑-垂体-性腺轴作用的临床和实验研究[J].中医杂志，1986（4）：33-37.
[10] 黎霄羽，姜迎，王小云.补肾法对去卵巢大鼠惊恐反应及海马雌激素受体β表达的影响[J].中华中医药杂志，2013，28（5）：404-407.
[11] 姚建平，牛巧能，李琳，等.左归丸、右归丸对自然衰老大鼠海马组织及齿状回NGF、FGF-2蛋白水平的影响[J].中成药，2018，40（8）：1836-1839.
[12] 刘宏，贾彦，仲丽丽，等.左归丸对惊恐伤肾MCAO大鼠BDNF及其受体的影响[J].中医药信息，2015，32（4）：10-14.
[13] Li M，Zhang Z，Sun W，et al. 17β-estradiol attenuates breakdown of blood-brain barrier and hemorrhagic transformation induced by tissue plasminogen activator in cerebral ischemia [J]. Neurobiol Dis，2011，44（3）：277-283.
[14] 关云谦，孙明，徐超.大鼠颈内动脉线栓法制备局灶性脑缺血模型及影响因素[J].国际脑血管病杂志，2001，9（3）：151-153.
[15] 丁实，赵学荣，李宝群，等.基于Bcl-2/Beclin-1复合体探讨黄连素对脑缺血再灌注损伤大鼠模型的保护作用[J].中国实验动物学报，2019，27（5）：651-657.
[16] Lee JY，Choi SY，Oh TH，et al. 17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury [J]. Endocrinology，2012，153（8）：3815-3827.
[17] Longa EZ，Weinstein PR，Carlson S，et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke，1989，20（1）：84-91.
[18] Garcia JH，Wagner S，Liu KF，et al. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats：statistical validation [J]. Stroke，1995，26（4）：627-635.
[19] Zaw JJT，Howe PRC，Wong RHX. Postmenopausal health interventions：Time to move on from the Women’s Health Initiative? [J]. Ageing Res Rev，2018，48：79-86.
[20] 刘宏，仲丽丽，张雨薇，等.左归丸对卵巢摘除MCAO模型大鼠CREB的影响[J].上海中医药杂志，2015，49（12）：61-64.
[21] 郝迪，刘宏，黄树明.左归丸对卵巢切除MCAO模型大鼠学习记忆功能的影响[J].中医药学报，2014，42（1）：122-124.
[22] Xue Q，Xiao D，Zhang L. Estrogen regulates angiotensin Ⅱ receptor expression patterns and protects the heart from ischemic injury in female rats [J]. Biol Reprod，2015，93（1）：1-9.
[23] Shin JA，Oh S，Ahn JH，et al. Estrogen receptor-mediated resveratrol actions on blood-brain barrier of ovariectomized mice [J]. Neurobiol Aging，2015，36（2）：993-1006.
[24] Keefe KM，Sheikh IS，Smith GM. Targeting neurotrophins to specific populations of neurons：NGF，BDNF，and NT-3 and their relevance for treatment of spinal cord injury [J]. Int J Mol Sci，2017，18（3）：548.
[25] Li Y，Li X，Guo C，et al. Long-term neurocognitive dysfunction in offspring via NGF/ERK/CREB signaling pathway caused by ketamine exposure during the second trimester of pregnancy in rats [J]. Oncotarget，2017，8（19）：30956.
[26] Barde YA，Edgar D，Thoenen H. Purification of a new neurotrophic factor from mammalian brain [J]. EMBO J，1982，1（5）：549-553.
[27] Bonni A，Brunet A，West AE，et al. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms [J]. Science，1999，286（5443）：1358-1362.
[28] Brunet A，Datta SR，Greenberg ME. Transcription-dependent and-independent control of neuronal survival by the PI3K-Akt signaling pathway [J]. Curr Opin Neurobiol，2001，11（3）：297-305.
[29] Moghbelinejad S，Nassiri-Asl M，Farivar T N，et al. Rutin activates the MAPK pathway and BDNF gene expression on beta-amyloid induced neurotoxicity in rats [J]. Toxicol Lett，2014，224（1）：108-113.
[30] Ola MS，Ahmed MM，Ahmad R，et al. Neuroprotective effects of rutin in streptozotocin-induced diabetic rat retina [J]. J Mol Neurosci，2015，56（2）：440-448.
[31] Meng X，Wang M，Wang X，et al. Suppression of NADPH oxidase-and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia-reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathways [J]. Free Radic Res，2014， 48（7）：823-838.
[32] Wang Y，Tu L，Li Y，et al. Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways [J]. J Pharmacol Expther，2016，357（3）：591-605. |
|
|
|
