机构地区:[1]辽宁中医药大学药学院,辽宁大连116600 [2]安徽济人药业股份有限公司,安徽亳州236800 [3]安徽省中药提取技术创新中心,安徽亳州236800 [4]国家中医药管理局中药炮制技术传承基地,辽宁大连116600 [5]辽宁省中药炮制技术产业创新中心,辽宁大连116600 [6]国家中医药管理局中药炮制工艺原理重点研究室,辽宁大连116600
出 处:《药学研究》2025年第2期105-112,共8页Journal of Pharmaceutical Research
基 金:国家自然科学基金项目(No.81874345);国家中医药管理局-重点实验室研究领域的中医临床疗效提升项目(2022年);辽宁省自然科学基金面上项目(No.2020-MS-223)。
摘 要:目的探究肉苁蓉炮制前后总多糖、总苷改善大鼠抑郁样行为的作用机制。方法将81只大鼠随机分为空白对照组(K)、模型组(M)、阳性药组(Y)、生品总多糖组(ST)、制品总多糖组(ZT)、生品总苷组(SG)、制品总苷组(ZG)、生品总多糖总苷联合给药组(SS)和制品总多糖总苷联合给药组(ZZ),除空白对照组外其他组每天皮下注射皮质酮以建立抑郁模型。记录大鼠体重并进行糖水偏好实验、旷场实验、强迫游泳实验等行为学测试;运用酶联免疫吸附测定(ELISA)法检测大鼠血清中促肾上腺皮质激素(ACTH)、白细胞介素-6(IL-6)、脑源性神经营养因子(BDNF)的水平,以及海马组织中5-羟色胺(5-HT)、花生四烯酰乙醇胺(AEA)、γ-氨基丁酸(GABA)的水平;RT-PCR法检测大鼠海马BDNF、酪氨酸激酶B(TrκB)、p-TrκB的mRNA表达情况;蛋白免疫印迹法检测大鼠海马BDNF、TrκB、p-TrκB和糖皮质激素受体(GR)蛋白表达情况。结果与模型组相比,生、制肉苁蓉给药组糖水偏好、旷场实验、强迫游泳等行为学指标改善,且均能降低大鼠血清中ACTH、IL-6含量,提高血清中BDNF、海马组织中5-HT、AEA、GABA的含量,以及升高BDNF、TrκB、p-TrκB的mRNA表达水平和增加BDNF、TrκB、p-TrκB和GR的蛋白表达。结论制肉苁蓉可增强抗抑郁作用,其作用机制可能与缓解炎症反应,改善中枢神经系统异常,激活BDNF/TrκB信号通路的传导相关。Objective To explore the mechanism of total polysaccharides and total glycosides of Cistanche deserticola before and after processing in improving depression-like behavior of rats.Methods 81 rats were randomly divided into blank control group(K),model group(M),positive drug group(Y),raw total polysaccharide group(ST),total polysaccharides of the processed Cistanche deserticola group(ZT),raw total glycoside group(SG),total glycosides of the processed Cistanche deserticola group(ZG),raw total polysaccharide total glycoside combined administration group(SS)and product total polysaccharide total glycoside combined administration group(ZZ).The depression model was established by daily subcutaneous injection of corticosterone in all groups except the blank control group.The body weight of rats was recorded and behavioral tests such as sucrose preference test,open field test and forced swimming test were performed.The levels of ACTH,IL-6,and BDNF in serum and 5-HT,AEA,and GABA in hippocampus were detected by enzyme-linked immunosorbent assay(Elisa).The mRNA expression of BDNF,TrκB and p-TrκB in hippocampus was detected by RT-PCR.The protein expressions of BDNF,TrκB,p-TrκB and GR in hippocampus were detected by Western blotting.Results Compared with the model group,the behavioral indicators such as sucrose preference,open field test and forced swimming of the raw and synthetic Cistanche deserticola treatment groups were significantly improved,and both of them could significantly reduce the serum levels of ACTH and IL-6 in rats,and increase the serum levels of BDNF and the hippocampal levels of 5-HT,AEA and GABA.The relative mRNA expression of BDNF,TrκB and p-TrκB was significantly increased,and the protein expression of BDNF,TrκB,p-TrκB and GR was significantly increased.Conclusion Processed Cistanches deserticola can enhance the antidepressant effect,and its mechanism may be related to alleviating inflammation,improving central nervous system abnormalities,and activating BDNF/TrκB signaling pathway.
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