Ethnopharmacological relevanceMenopausal syndrome (MPS) is a symptom of physical and psychosomatic abnormalities that women may face around the time of menopause. Hot flashes are the main symptom. Paeonia lactiflora extract (PLE) is the active ingredient extracted from Radix Paeonia alba. It can be used to treat MPS, such as hot flashes. However, its pharmacologic mechanism is unclear.Aim of the studyThis study aims to comprehensively evaluate the effect of PLE on menopausal hot flashes, and to analyze the mechanism of action of PLE in the treatment of menopausal hot flashes from the perspective of neural pathways, to provide a research strategy and experimental basis for the study of similar new drugs and the pathogenesis of MPS.Materials and methodsFirst, we screened menopausal rats through the natural aging model. After 14 days of therapeutic drug gavage, a menopausal hot flashes model was induced in menopausal rats by gavage with thyroid tablet suspension (160 mg/kg) for 14 days. The changes in facial and tail temperature of rats in each group were observed; the behavioral characteristics of rats in each group were followed by an open field test, elevated plus maze and aggressive behavior test; the contents of estradiol, luteinizing hormone, follicle stimulating hormone, 5-hydroxytryptamine, cyclic guanosine monophosphate and cyclic adenosine monophosphate were detected by ELISA; the pathological changes of the uterus were detected by HE staining method. Combined with transcriptomics technology, high-throughput transcriptome sequencing was performed on the hypothalamus of control, model and PLE (160 mg/kg) group, and differential gene analysis between control and model groups, and PLE (160 mg/kg) group and model group was performed using DESeq2. qRT-PCR and Western blot were used to further validate the candidate core genes.ResultsPLE improved the mental status of model rats and reduced the abnormal tail temperature elevation in model rats. In addition, PLE had the effect of increasing the estradiol content and decreasing the luteinizing hormone content in the serum of rats, and the administration of 160 mg/kg of PLE also significantly increased the 5-hydroxytryptamine content in the serum of rats. In terms of pathological manifestations, the model rats had significantly thinner endometrial thickness, looser tissues and reduced integrity, while the rats intervened by PLE treatment had significantly thicker endometrium and more regularly arranged tissue structure. Therefore, it can be determined that PLE has a good pharmacological basis for the treatment of menopausal hot flashes. The transcriptomic analysis showed that 210 genes were significantly altered in the control and drug administration groups together, and the candidate core genes related to neuroendocrine were screened out based on the comprehensive literature and previous studies, and it was further found that PLE may achieve ASIC4, cplx1, mRNA expression levels, and Tac3, Tacr3 protein expression levels by up-regulating neuroprotective effects, thereby restoring the normal neuroendocrine environment of menopausal hot flashes in rats.ConclusionPLE can effectively alleviate thyroid tablet-induced menopausal hot flashes, and the mechanism may be related to the regulation of abnormal expression of ASIC4, cplx1, GnRH1, Tac3, and Tacr3 in the hypothalamus, thereby restoring the imbalanced hypothalamic-pituitary-gonadal axis.

Objective We determined whether the pathogenesis of perimenopausal depression (PMD) is associated with allopregnanolone (3α,5α-THP, ALLO) mediated GABAA receptors subunits expression changes in different brain regions. Simultaneously, we aimed to investigate the therapeutic efficacy and intervention mechanisms of the flavonoid rutin in treating PMD. Methods The PMD rat model was established by ovariectomy surgery followed by chronic unpredictable mirutin stress processes. ALLO was administered via intraperitoneal injection to increase ALLO levels in PMD rats, while rutin was administered via oral gavage for PMD treatment. Behavioral assessments, including open-fierutin test, sucrose preference test, and forced swimming test, were conducted to evaluate depressive-like behaviors in rats. ELISA was employed to measure the levels of E2, 5-HT, NE, ALLO, and GABA in the serum. Quantitative PCR was used to assess the mRNA expression of Gabra4, Gabrb2, and Gabrd in the prefrontal cortex, hippocampus, hypothalamus, and amygdala. Results The PMD rats exhibited depressive-like behavior, with decreased levels of E2, 5-HT, NE, ALLO, and GABA in the serum. The mRNA expression of Gabra4 and Gabrb2 increased in the prefrontal cortex, hippocampus, and hypothalamus of PMD rats, while Gabrd showed a increase in the hypothalamus and amygdala. ALLO improved depressive-like behavior and increased serum levels of E2, 5-HT, NE, and ALLO in PMD rats. ALLO acted on PMD rats, reduced mRNA expression of Gabra4 and Gabrb2 in the prefrontal cortex, increased mRNA expression of Gabrd in the prefrontal cortex, elevated mRNA expression of Gabra4 and Gabrd in the hippocampus, and decreased Gabrb2 mRNA expression in the hypothalamus.Rutin improved depressive-like behavior in PMD rats, increased serum levels of 5-HT and ALLO, and decreased mRNA expression of Gabra4 and Gabrb2 in the prefrontal cortex. Conclusion ALLO-mediated mRNA expression of Gabra4, Gabrb2 in the prefrontal cortex, and Gabrb2 in the hypothalamus is one of the pathological mechanisms in PMD. ALLO can improve depressive symptoms in PMD rats. Rutin (8.65 mg/kg) exerts a therapeutic effect on PMD by upregulating serum ALLO levels, subsequently downregulating mRNA expression of prefrontal cortex Gabra4 and Gabrb2.

目的:比较不同肾阴虚证动物模型造模方法,筛选有效可靠的肾阴虚证模型制备方法.方法:KM种雌性小鼠40只,按体质量随机分为对照组、甲状腺片组、甲状腺片联合利血平组(联合组)、氢化可的松组,每组10只.对照组每天给予生理盐水灌胃,甲状腺片组灌胃甲状腺片160 mg·kg-1,联合组灌胃甲状腺片150 mg-kg-1及利血平1 mg-kg-1,氢化可的松组灌胃氢化可的松注射液50 mg-kg-1,建立三种肾阴虚证模型小鼠.分别观察各组小鼠进食量、饮水量、体质量、活动情况、面温、尾温、血清环磷酸腺苷(cAMP)与环磷酸鸟苷(cGMP)含量变化,考察三种肾阴虚证模型小鼠体质量及自身能量代谢差异.根据小鼠实验结果,在雌性SD大鼠上进行模型验证及筛选,确定最佳模型制备方法.结果:小鼠实验显示,三种模型造模结束后,与对照组比较,造模小鼠饮水与进食量均增加,体质量均有不同程度的降低,活动量均减少,其中甲状腺片组小鼠面温、尾温显著升高(P＜0.05),且体质量变化率较对照组低(P＜0.05),血清cAMP含量显著升高(P＜0.05),cGMP含量有升高趋势,卵巢、子宫及肾上腺等脏器变化较小;联合组小鼠面温及尾温无显著性变化,但体质量变化率较对照组低(P＜0.05),血清cGMP含量显著降低(P＜0.05),子宫、卵巢及肾上腺等脏器变化较大;氢化可的松组小鼠体质量变化率较对照组显著降低(P＜0.05),且肾上腺组织脏器指数显著变化(P＜0.05).大鼠实验显示,与对照组比较,造模大鼠饮水与进食量均增加,体质量均有不同程度的降低,活动量均减少,面温及尾温显著升高(P＜0.05),体质量变化率显著降低(P＜0.05),血清cGMP含量显著升高(P＜0.05).结论:甲状腺片灌胃小鼠及大鼠均可以较好地制备肾阴虚动物模型,肾阴虚证模型表征明显,稳定性高,操作简单,且对子宫、卵巢、肾上腺等脏器影响较小,可用于中医药相关领域的深入研究.

围绝经期是女性从中年步入老年的重要转折,在这个阶段由于社会、心理、生理等因素的交互作用,女性患围绝经期抑郁症的风险大大增加,因此,围绝经期抑郁症发病机制的研究备受关注.由于海马区为机体学习记忆、方向辨识以及情绪调节等功能的重要区域,在抑郁症发病以及抗抑郁药物发挥疗效中起着重要作用.文献查阅发现,关于围绝经期抑郁症发病机制目前主要集中在中枢海马脑源性神经营养因子信号通路、环磷酸腺苷通路、丝裂原活化蛋白激酶通路以及钙调蛋白激酶等通路上.本文主要从以上通路入手综述围绝经期抑郁症的主要发病机制.

目的 利用超声技术,确定大鼠甲状腺定位,同时分析评价大鼠结节性甲状腺肿模型的病变、造模程度,为结节性甲状腺肿及相关甲状腺疾病大鼠模型的诊断评估提供技术方法.方法 40只6～8周龄SPF级Wistar大鼠,雌雄各半,其中20只作为对照组,其余大鼠灌服丙基硫氧嘧啶(PTU)溶液8周,构建结节性甲状腺肿大鼠模型,造模结束后对大鼠进行甲状腺超声检测,同时进行病理检测,与超声结果进行对比.结果 超声检测显示,模型组大鼠甲状腺前后、内外侧径均显著大于对照组(P<0.001),同时可见模型组大鼠腺体不对称性增大,甲状腺侧叶有结节无包膜,边界较为模糊,不规整,散在有点状或条状纤维增生的强回声.模型组大鼠甲状腺切片HE染色显示,甲状腺组织形状、滤泡大小均不规则,差异较大,且上皮细胞增生明显,排列紊乱,胶质压缩且分布不均.模型组大鼠的超声和病理学检测均符合疾病诊断.结论 超声检测技术可以较好地进行活体评价大鼠结节性甲状腺肿动物模型,是值得推广的结节性甲状腺肿大鼠模型的评价方法.

Background: Perimenopausal depressive disorder (PDD) is an affective disorder involving endocrine, neurological, immune, which seriously endangers the physical and mental health of human. Selective serotonin reuptake inhibitors (SSRIs) are the current first-line clinical treatment, have limited efficacy and serious side effects. Acupuncture combined with SSRIs therapy has been widely used clinically because it increases efficacy and reduces side effects. There is a lack of high-quality evidence to assess its efficacy and safety. This study evaluated the effectiveness and safety of acupuncture combined with SSRIs in the treatment of PDD by meta-analysis. Methods: All randomized controlled trials articles about acupuncture combined with SSRIs treatment of PDD will be searched in databases, such as PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, Wei Pu from the construction of the library to December 16, 2021. According to Cochrane 5.1 Handbook criteria, two researchers independently screened the literature, extracted data, and evaluated the quality of included studies. Meta-analysis was performed by using RevMan 5.4 and STATA 16.0 software. Results: This study will summarize the current evidence to evaluate the effectiveness and safety of acupuncture combined with SSRIs for the treatment of PDD. Conclusion: The results of this study will provide clinicians with new treatment ideas and bring benefits to most patients. Registration number: INPLASY2021120080 (DOI number: 10.37766/inplasy2021.12.0080).

抑郁症是一种以持续心境低落为主要特征的疾病,具有很高的复发率和自杀率,严重危害人类健康.目前主要采用西医进行抗抑郁治疗,但由于抗抑郁西药的不良反应日渐凸显,使的中药成为抗抑郁治疗的热点.药对是中药配伍中的最小单位,是中药复方的核心.药对作为单味中药与复方之间的桥梁,是历代医家在遣方用药中的经验总结.从中药药对的角度着手,探索药对在抗抑郁治疗中发挥的作用具有重要的意义.对常见的抗抑郁药对进行阐述,以期为中药的抗抑郁治疗提供新的思路和方法.

目的：探讨贞芍组方对围绝经期模型小鼠下丘脑-垂体-卵巢轴（HPO轴）关键因子的保护作用。方法：选取175只11月龄雌性ICR小鼠和15只7-8周龄且动情周期规律的雌性ICR小鼠。采用11月龄雌性ICR小鼠制备围绝经期小鼠模型，按体重随机数字表法分为戊酸雌二醇组、坤宝丸组、溶媒组、贞芍配伍组。利用旷场及高架十字迷宫实验等行为学实验；ELISA法检测血清中激素和神经递质的含量；HE染色法观察子宫、卵巢的形态；免疫荧光法检测子宫、卵巢中雌激素受体（Estradiol receptor， ER）的表达。结果：与对照组相比，模型小鼠表现出明显的抑郁焦虑行为，表现为自发活动和探索行为减少；血清中雌二醇（Estradiol，E2）含量显著性降低（P＜0.05），卵泡刺激素（Follicle-stimulating hormone， FSH）含量显著性升高（P＜0.01）；神经递质五羟色胺（5-hydroxytryptamine，5-HT）含量显著性降低（P＜0.05）；子宫、卵巢的ERβ表达显著性降低（P＜0.01，P＜0.05）等。同时经贞芍组方给药，明显发现小鼠围绝经期综合征症状明显改善，各配伍组组间比较，以36.1mg/kg和288.8mg/kg组较为明显。结论：贞芍组方可通过改善血清中E2、FSH的分泌水平，促进子宫、卵巢组织中ERβ蛋白的表达，有效改善子宫、卵巢功能，纠正围绝经期模型小鼠失衡的HPO轴；同时能够增加小鼠探索行为、降低焦虑水平，说明贞芍组方可能还具有改善不良情绪的作用。