摘要
目的:探讨云南藤黄乙醇标准提取物(YTE-17)抑制结直肠癌转移的作用效果及其潜在机制。方法:采用克隆形成实验观察YTE-17对结直肠癌细胞HCT116和LoVo的生长和增殖情况;划痕和Transwell实验检测YTE-17对结直肠癌侵袭迁移能力的影响;蛋白质免疫印迹法(Western blot)检测YTE-17对基质金属蛋白酶-2(MMP-2)、生存素(Survivin)、细胞周期蛋白D1(cyclin D1)、E-钙黏着蛋白(E-cadherin)和波形蛋白(Vimentin)表达的调节作用。结果:YTE-17可显著抑制结直肠癌细胞HCT116和LoVo的生长和增殖;与对照组(YTE-17干预0μg/mL)比较,YTE-17能够抑制HCT116和LoVo细胞侵袭迁移能力(P<0.01),且呈浓度依赖性。Western blot结果显示,YTE-17可以降低HCT116细胞中Survivin、Cyclin D1和E-cadherin的表达,并呈剂量依赖性(P<0.01);YTE-17可以降低LoVo细胞中Survivin、Cyclin D1、MMP-2和Vimentin的表达,并呈剂量依赖性(P<0.01)。结论:YTE-17可通过降低Survivin、Cyclin D1、MMP-2、E-cadherin和Vimentin表达抑制结直肠癌的侵袭转移。
Objective:To explore the relevant biological mechanisms of Jieyu Formula(JYF)in treating post-stroke depression(PSD).Methods:60 healthy male SPF SD rats were randomly divided into sham-operated group,stroke group(MCAO group),poststroke depression group(PSD group),JYF low-dose group,JYF high-dose group and fluoxetine group after behavioral scoring.The MCAO group was modeled by the middle cerebral artery occlusion(MCAO)method,and the PSD group,JYF low-dose group,JYF high-dose group and fluoxetine group were modeled by MCAO+chronic unpredictable mild stress(CUMS)method+solitary feeding method for poststroke depression.Body mass and behavioral tests were performed at 0,3,5,and 7 weeks respectively.After 7 weeks,immunohistochemistry was used to detect the expression of cannabinoid type 1 receptor(CB1R)/cannabinoid type 2 receptor(CB2R)and corticotropin-releasing factor(CRF)in the hippocampus of rats in each group.Results:Body mass test results showed that before administration,compared with the sham-operated group,the body mass of the PSD group,JYF high-dose group,JYF low-dose group and fluoxetine group was significantly reduced(P<0.05);after administration,compared with the PSD group,the body mass of the JYF highdose group and fluoxetine group was significantly increased(P<0.05).Forced swimming experiment results showed that before administration,compared with the sham-operated group,the immobility time of forced swimming in the PSD group,JYF high-dose group,JYF low-dose group and fluoxetine group was significantly increased(P<0.05)and the struggling time of forced swimming was significantly reduced(P<0.05);after administration,compared with the PSD group,the immobility time of forced swimming in the JYF low-dose group,JYF high-dose group and fluoxetine group was significantly reduced(P<0.05)and the struggling time of forced swimming was significantly increased(P<0.05).Sucrose preference test results showed that before administration,compared with the sham-operated group,the sucrose preference of the PSD group,JYF high-dose group,JYF low-dose group and fluoxetine group was significantly decreased(P<0.05);after administration,compared with the PSD group,the sucrose preference of the JYF low-dose group,JYF high-dose group and fluoxetine group was significantly increased(P<0.05).Immunohistochemistry results showed that compared with the sham-operated group,the expression of hippocampal CB1R and CB2R in hippocampal subfields(CA1,CA3 and DG)was significantly decreased in the PSD group(P<0.05),and the expression of hippocampal CRF in CA1,CA3 and DG regions was significantly increased in the PSD and MCAO groups(P<0.05).Compared with the PSD group,CB1R expression in CA1,CA3 and DG regions was significantly increased in the JYF low-dose group,JYF high-dose group and fluoxetine group(P<0.05),CB2R expression in CA1,CA3 and DG regions was significantly increased in the JYF high-dose group and fluoxetine group(P<0.05),CB2R expression in CA1 and DG regions was significantly increased in the JYF low-dose group(P<0.05),CRF expression in CA1,CA3 and DG regions was significantly decreased in the JYF low-dose group,JYF high-dose group and fluoxetine group(P<0.05).Conclusion:JYF can significantly improve the depression-like behavior and play a neuroprotective role in PSD rats,and its mechanism of action may be related to the up-regulation of CB1R and CB2R expression and the down-regulation of CRF expression in hippocampus.
作者
柴琼
张璐
李波旺
巩伟伟
段琳琳
隋华
CHAI Qiong;ZHANG Lu;LI Bowang;GONG Weiwei;DUAN Linlin;SUI Hua(School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Combine Traditional Chinese&Western,The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer Hospital,Zhengzhou 450008,Henan,China;Graduate School,Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China;Department of Metabolism and Nephrology Rehabilitation,The First Rehabilitation Hospital of Shanghai,Shanghai 200090,China;Medical Experiment Center,Jiading Branch of Shanghai General Hospital,Shanghai 201803,China)
出处
《上海中医药大学学报》
CAS
2024年第6期47-56,共10页
Academic Journal of Shanghai University of Traditional Chinese Medicine
基金
上海市嘉定区科委科研项目(JDKW-2021-0029)
河南省中医药科学研究专项课题(2024ZY2145,2022ZY1223)。
作者简介
柴琼,女,硕士,助理研究员,主要从事中药抗肿瘤药理学研究;通信作者:隋华,副研究员,E-mail:syh0808@163.com。