Study on prevention effect of Zishen Yutai pill combined with progesterone for threatened abortion in rats

Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group(P<0.05).The maternal-fetal interface IL-4/IL-2,IL-10 / IL-2 of model group were balanced deviating to Th1,while the IL-4/IL-2,IL-10/IL-2 of progesterone group,Zishen Yutai pill group and joint group were balanced deviating to Th2,and joint group' deviation was better than progesterone group and Zishen Yutai pill group(P<0.05).Conclusions:Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion,which can obviously increase contents of maternal serums E2 and P,and regulate the Thl/Th2 balance with a remarkable effect.

Effects of Chinese Patent Drug Zishen Pills in Treatment of Elderly Patients with Impaired Glucose Tolerance(IGT)

[Objectives]To evaluate the efficacy of Zishen Pills(ZSP),a Chinese patent drug,in the treatment of elderly patients with impaired glucose tolerance(IGT)and its effects on the prevention of diabetes mellitus(DM).[Methods]Thirty-five IGT patients were randomized to receive 10 g of ZSP three times daily(ZSP group,n=24)or no drug intervention(control group,n=11)for 12 weeks.Oral glucose tolerance test,glycated hemoglobin A1c(HbA1c),body mass index,blood lipids levels,fasting insulin,and insulin resistance calculated using homeostatic model assessment(HOMA-IR)of all the patients were observed and compared before and after the treatment.[Results]Thirty participants completed the trial(20 in ZSP group and 10 in the control group).There were statistically significant decreases in plasma triglycerides(TG),fasting blood-glucose(FBG),2-h plasma glucose(2-h PG),HbA1c,and HOMA-IR in ZSP group compared with the control group after 12 weeks of treatment(P<0.05 or P<0.01).After 12 weeks of treatment,2(20.0%)patients returned to normal blood glucose,and 2(20.0%)patients turned into DM in control group,while in the ZSP group,9(45.0%)patients returned to normal blood glucose and 1(5.0%)patient turned into DM.[Conclusions]ZSP effectively improved glucose control,increased the conversion of IGT to normal glucose,and improved the insulin resistance in elderly patients with IGT.This Chinese patent drug may have a clinical value for IGT.

Regulation of Zishen Qinggan( Shuangyi) Prescription to Insulin Resistance of GK Rats

[Objective] To study the effects of Zishen Qinggan( Shuangyi) Prescription on blood glucose,Hb A1c( glycosylated hemoglobin A1c),C-peptide( C-P),glucagon-like peptide( GLP-1),and α-glucosidase activity in GK( Goto-Kakizaki) rats. [Methods]Selected fasting blood glucose( FBG) > 11. 1mmol/L GK rats and randomly divided into groups: model group,Zishen Qinggan( Shuangyi) Prescription low dosage( ig,400 mg/kg/d),medium dosage( ig,800 mg/kg/d),and high dosage groups( ig,1600 mg/kg/d),and metformin group(ig,85 mg/kg/d). After continuous administration for 28 d,fasting blood glucose(FBG),oral glucose tolerance test(OGTT),Hb A1 c,C-P,GLP-1 and α-glucosidase activity were detected. [Results] Compared with the control group,FBG and Hb A1 c of the model group was significantly higher( P < 0. 01); compared with the model group,Zishen Qinggan( Shuangyi) Prescription could significantly reduce the levels of blood glucose,Hb A1 c,and the elevated blood glucose levels after 120 min of glucose loading in OGTT( P < 0. 05,P < 0. 01),and also can significantly improve the level of C-P,GLP-1( P < 0. 05,P < 0. 01),reduce Homa-IR,and inhibit α-glucosidase activity. [Conclusions]Zishen Qinggan( Shuangyi) Prescription can effectively reduce the blood glucose of GK rats,the action mechanism of which is possibly that it can improve insulin resistance,increase GLP-1 content and inhibit α-glucosidase activity.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve:A Prospective,Open-Labeled,Randomized and Controlled Study

Objective:To explore the effects of Zishen Yutai Pills(ZYPs)on the quality of oocytes and embryos,as well as pregnancy outcomes in patients with diminished ovarian reserve(DOR)receiving in vitro fertilizationembryo transfer(IVF-ET).The possible mechanisms,involving the regulation of bone morphogenetic protein 15(BMP15)and growth differentiation factor 9(GDF9),were also investigated.Methods:A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio.The patients in the treatment group(60 cases)received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone(Gn RH)antagonist protocol.The patients in the control group(60 cases)received the same protocol but without ZYPs.The primary outcomes were the number of oocytes retrieved and high-quality embryos.Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes.Adverse events were assessed by comparison of the incidence of ectopic pregnancy,pregnancy complications,pregnancy loss,and preterm birth.Contents of BMP15 and GDF9 in the follicle fluids(FF)were also quantified with enzymelinked immunosorbent assay.Results:Compared with the control group,the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group(both P<0.05).After treatment with ZYPs,a significant regulation of serum sex hormones was observed,including progesterone and estradiol.Both hormones were up-regulated compared with the control group(P=0.014 and 0.008),respectively.No significant differences were observed with regard to pregnancy outcomes including implantation rates,biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and pregnancy loss rates(all P>0.05).The administration of ZYPs did not increase the incidence of adverse events.The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group(both P<0.05).Conclusions:ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET,resulting in increments of oocytes and embryos,and up-regulation of BMP15 and GDF9 expressions in the FF.However,the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes(Trial reqistration No.Chi CTR2100048441).

Ningxin Tongyu Zishen Tang in Treatment of Premature Ovarian Insufficiency:A Retrospective Control Study

Background:Premature ovarian insufficiency(POI)is a common refractory disease in gynecology,and its etiology and pathogenesis are complex.Psychological stress exerts an impact on women’s physical and mental health,and in turn affects the ovarian reserve function,which is one of the important etiologies and pathogenesis of POI.The compound formula Ningxin Tongyu Zishen Tang(NTZT)is composed of Chinese herbal medicines which can nourish heart and tranquilize mind,tonify kidney and supplement essence.By comparing the menstrual symptoms,traditional Chinese medicine(TCM)symptoms and the levels of serum sex hormone before and after treatment,the NTZT is clarified for its curative effect and advantages in patients with POI.Objective:The study aimed to observe the effects of NTZT on menstrual symptoms,TCM symptoms and the levels of serum sex hormone in POI patients.Methods:60 POI patients were divided into two groups,namely observation group and control group,with 30 patients in each group.The patients in both groups were treated by hormone replacement therapy(HRT).The observation and control groups received treatment with NTZT and or Liuwei Dihuang Wan(LDW),respectively.All of the patients were treated for 3 months continuously.The menstrual symptoms,TCM symptoms and the levels of serum sex hormone of the two groups were investigated before and after treatment.Results:It was found that the menstrual symptoms,TCM symptoms and the levels of serum sex hormone improved dramatically after treatment in the observation group(P<0.01).By comparison,the menstrual symptoms and the levels of serum sex hormone improved significantly(P<0.01),but no obvious improvement in TCM symptoms(P>0.05)in the control group was observed.Compared with the control group,the observation group showed significant improvement in TCM symptoms and the levels of serum sex hormone(P<0.01),but no significant difference was observed in the menstrual symptoms(P>0.05).In addition,there was no any adverse events such as gastrointestinal dysfunction and drug allergyobserved in both groups,indicating the safety of the two TCM formulas.Conclusion:The study found that NTZT could restore menstruation and improve the levels of sex hormone in patients with POI.It was also found that NTZT could eliminate the feelings of vexation,insomnia and dream-fulness,as well as tidal fever and sweating,aching pain of loins,and vaginal dryness significantly.It can be proved that NTZT is effective in treating patients with POI owing to its effects of nourishing heart and tranquil-izing mind,tonifying kidney and supplementing essence together,leading to elimination of psychological stress,which further promotes the development of the ovaries.

滋肾通淋排石汤辅助治疗在肾结石术后患者中的应用及机制

目的探讨滋肾通淋排石汤辅助治疗在肾结石术后患者中的应用及机制。方法选取该院2021年2月—2022年2月收治的肾结石术后患者202例,按照随机数字表法分为对照组和观察组各101例。两组患者均给予常规的输尿管软镜碎石术进行治疗,术后给予对照组患者常规体位排石治疗,观察组患者在对照组基础上给予滋肾通淋排石汤联合进行治疗,两组均治疗2周。比较两组治疗后的临床疗效,治疗前后的中医证候积分、肾功能、炎性应激指标水平,不同时点的视觉模拟评分(visual analog scale,VAS)。结果治疗后观察组临床总有效率高于对照组;与治疗前比较,治疗后两组尿频、腰痛、少腹急满、血尿、淋漓不爽评分及血清β2微球蛋白(β2 microglobulin,β2-MG)、肌酐(serum creatinine,Scr)、中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、尿素氮(blood urea nitrogen,BUN)、白细胞介素-10(interleukin-10,IL-10)、超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)、高迁移率族蛋白-1(high mobility group box-1 protein,HMGB1)、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)水平均降低,观察组低于对照组;与治疗前比较,治疗3 d~2周后两组VAS评分呈逐渐降低趋势,观察组低于对照组,差异均有统计学意义(均P<0.05)。结论滋肾通淋排石汤应用于肾结石术后患者,可以减轻疼痛,改善肾功能,抑制炎症反应和应激反应,提升临床治疗效果。

滋肾活血方对血管性痴呆大鼠认知功能障碍的治疗作用

目的 探究滋肾活血方改善血管性痴呆(vascular dementia, VD)大鼠认知功能障碍的分子机制。方法 采用双侧颈总动脉闭塞法(bilateral common carotid artery occlusion, BCCAO)构建VD大鼠模型,随机分为假手术组(sham组)、模型组(VD组)、滋肾活血方高剂量组(15.2 g/kg)、滋肾活血方中剂量组(7.6 g/kg)、滋肾活血方低剂量组(3.8 g/kg)、奥拉西坦组(阳性对照)。通过Morris水迷宫实验记录大鼠的逃避潜伏时间以及穿越平台的次数评估大鼠认知功能;HE染色观察海马组织病理学改变和炎性浸润;尼氏染色评估海马神经元损伤;免疫荧光检测海马组织小胶质细胞M1/M2极化情况;ELISA试剂盒检测海马组织促炎因子(TNF-α、IL-1β)和抗炎因子(TGF-β、IL-4)的水平;Western blot法检测TLR4、p65核蛋白水平。结果 与sham组相比,VD组大鼠逃避潜伏期延长(P<0.001),穿越平台次数减少(P<0.001),海马神经元排列不规则,炎性细胞浸润增多,Iba-1、CD16/32以及CD206的水平,促炎因子(TNF-α、IL-1β),抗炎因子(TGF-β、IL-4)水平以及TLR4和p65核蛋白水平均显著升高(P<0.001)。与VD组相比,滋肾活血方高、中、低剂量组和奥拉西坦组大鼠的逃避潜伏期缩短(P<0.05),穿越平台次数增加(P<0.01),大鼠神经元病理变化得到改善,Iba-1、CD16/32以及CD206的水平,促炎因子(TNF-α、IL-1β)以及TLR4和p65核蛋白水平的表达均明显降低(P<0.01),抗炎因子(TGF-β、IL-4)水平上调(P<0.01)。结论 滋肾活血方通过抑制TLR4/NF-κB信号通路促进小胶质细胞M2型极化缓解VD大鼠认知功能障碍。

滋肾通关方对糖尿病大鼠肾损伤的改善作用及其机制

目的:研究滋肾通关方对糖尿病大鼠肾损伤的改善作用及其机制。方法:将50只8周龄雄性SD大鼠随机分为5组(每组10只):对照组、模型组和滋肾通关方低剂量(7.0 g生药/kg)、中剂量(14.0 g生药/kg)、高剂量(28.0 g生药/kg)组。除对照组外,其余组大鼠高脂高糖喂养4周联合腹腔注射链脲佐菌素(STZ,35 mg/kg)构建糖尿病肾损伤大鼠模型。造模成功后,各组分别连续4周灌胃给予相应药物或生理盐水,1次/d。给药前和给药后第1、2、3、4周检测空腹血糖(FBG)、血清尿素氮(BUN)、肌酐(Cr)、总胆固醇(TC)、三酰甘油(TG)含量,酶联免疫吸附试验(ELISA)测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)含量;苏木精-伊红(HE)染色法观察肾损伤情况,蛋白质印迹法检测肾组织转化生长因子-β_(1)(TGF-β_(1))/Smads通路相关蛋白的表达。结果:与对照组比较,模型组的大鼠FBG和血清BUN、Cr、TC、TG、TNF-α、IL-6、IL-1β均显著升高(均P<0.05);肾组织可见病理学损伤改变;TGF-β_(1)、Smad3、α-平滑肌肌动蛋白(α-SMA)和波形蛋白(Vimentin)的表达明显上调,而Smad7的表达明显下调。滋肾通关方低、中、高剂量组治疗4周后糖尿病肾损伤大鼠FBG和血清BUN、Cr、TC、TG、TNF-α、IL-6、IL-1β含量均明显降低(均P<0.05),肾组织病理学损伤明显改善,TGF-β_(1)、Smad3、α-SMA、Vimentin表达下调且Smad7表达上调,在不同剂量的滋肾通关方观察组中,其作用表现出一定的剂量依赖性。结论:肾通关方可通过抑制TGF-β_(1)/Smads信号通路改善糖尿病大鼠肾纤维化损伤。

滋肾育胎丸联合盐酸屈他维林片治疗绒毛下血肿的效果研究

目的:探讨滋肾育胎丸联合盐酸屈他维林片治疗绒毛膜下血肿(SCH)的临床效果,并观察治疗前后调节性T细胞/辅助性T细胞17(Treg/Th17)表达情况。方法:选取2023年1月至2023年12月新疆医科大学第一附属医院收治的早期先兆流产合并SCH,并伴有下腹痛和阴道流血的97例患者作为研究对象,采用随机数字表法随机分为观察组(n=47)和对照组(n=50)。对照组单纯给予屈他维林治疗;观察组在对照组的基础上加用滋肾育胎丸进行治疗。比较2组患者的一般临床资料、临床治疗有效率、止血止痛相关指标、治疗前后绒毛膜下血肿超声检测结果及治疗前后外周血Treg/Th17表达水平。结果:2组治疗后的绒毛膜下血肿面积/孕囊面积均低于治疗前(P<0.01),且观察组低于对照组(P<0.01)。观察组止血控制时间短于对照组(P<0.01);观察组临床治疗有效率高于对照组(P<0.05)。治疗后2组患者TGF-β水平高于治疗前,且IL-17水平低于治疗前(P<0.01);治疗后观察组TGF-β水平高于对照组,而IL-17水平低于对照组(P<0.01)。结论:滋肾育胎丸联合盐酸屈他维林片在早孕期SCH患者中的临床应用效果显著,提高临床治疗有效率,促进T细胞向Treg转化。

滋肾育胎丸联合贝米肝素钠治疗肾虚血瘀型复发性流产的临床观察

目的探讨滋肾育胎丸联合贝米肝素钠治疗肾虚血瘀型复发性流产(recurrent spontaneous abortion,RSA)的临床效果。方法选取2021年1月至2023年6月江西省妇幼保健院收治的98例肾虚血瘀型RSA患者,随机分为观察组和对照组,每组49例。对照组患者予贝米肝素钠治疗,观察组患者加用滋肾育胎丸治疗。比较两组患者的临床疗效、中医证候积分、性激素水平、子宫动脉血流参数、保胎情况及不良反应。结果治疗后观察组总有效率高于对照组(P<0.05);屡孕屡堕、腰骶酸痛、阴道流血、双膝酸软积分低于对照组(P<0.05);孕酮、人绒毛膜促性腺激素、雌二醇水平高于对照组(P<0.05);子宫动脉阻力指数、收缩期与舒张期流速比、脉搏动指数低于对照组(P<0.05);保胎成功率、活产率高于对照组(P<0.05);两组患者的不良反应比较,差异无统计学意义(P>0.05)。结论滋肾育胎丸联合贝米肝素钠可提高RSA患者的疗效,改善患者的性激素水平,利于保胎,提高最终活产率。

基于网络药理学与分子对接技术探讨滋肾养血活血汤治疗胚胎反复种植失败作用机制

目的:通过网络药理学和分子对接技术探讨滋肾养血活血汤治疗胚胎反复种植失败(RIF)的作用机制。方法:利用中药系统药理数据库和分析平台(TCMSP)查找滋肾养血活血汤组成药物的化学成分,并筛选出有效活性成分及有效活性成分的作用靶点,通过GeneCards和人类在线孟德尔遗传(OMIM)数据库筛选RIF疾病靶点,将药物有效活性成分作用靶点与RIF疾病靶点取交集,借助String平台制作蛋白质-蛋白质互作(PPI)网络,然后利用Cytoscape3.9.1软件进行网络结构的拓扑分析筛选核心靶点,并构建中药-活性成分-靶点可视化网络图,利用DAVID在线数据库对核心靶点进行富集分析,采用AutoDock Vina软件对筛选出的主要药物有效活性成分和疾病关键靶点进行分子对接验证。结果:共获得122个药物有效活性成分和256个药物作用靶点,疾病相关靶点2215个,药物-疾病核心靶点36个。经筛选获得5个主要药物有效活性成分与9个疾病关键靶点。京都基因与基因组百科全书(KEGG)富集分析结果显示,滋肾养血活血汤治疗RIF可能主要通过调控缺氧诱导因子-1(HIF-1)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶(MAPK)等多种信号通路发挥治疗作用。分子对接结果表明,β-谷甾醇与蛋白激酶B1(AKT1)、丹参酮ⅡA与HIF-1A、丹参酮ⅡA与TNF、槲皮素与HIF-1A对接活性较好。结论:滋肾养血活血汤可能通过槲皮素、山柰酚、木犀草素、β-谷甾醇、丹参酮ⅡA等与靶蛋白相互结合,调控多种信号通路发挥治疗RIF的作用。

健脾滋肾汤治疗系统性红斑狼疮对患者血清炎性因子、凝血功能及免疫功能的影响

目的 探究系统性红斑狼疮患者采用健脾滋肾汤治疗的效果。方法 选取86例系统性红斑狼疮患者,采用随机数字表法分为对照组和观察组,每组43例。对照组采用常规治疗,观察组在对照组基础上采用健脾滋肾汤治疗。对比两组患者的治疗效果。结果 治疗后,观察组免疫球蛋白A(IgA)(1.64±0.53)g/L、免疫球蛋白G(IgG)(10.28±2.39)g/L低于对照组的(2.05±0.72)、(12.43±1.52)g/L,补体C3、补体C4(106.31±12.17)、(21.94±5.32)mg/L高于对照组的(90.36±11.87)、(18.37±4.62)mg/L,差异有统计学意义(P<0.05),两组患者免疫球蛋白M(IgM)水平对比,差异无统计学意义(P>0.05)。治疗后,观察组凝血酶时间(TT)(18.74±1.17)s短于对照组的(20.29±1.73)s,纤维蛋白原(FIB)水平(3.41±0.35)g/L低于对照组的(4.16±0.48)g/L,凝血酶原时间(PT)(12.19±0.47)s、活化部分凝血活酶时间(APTT)(32.39±1.83)s长于对照组的(10.75±0.61)、(29.78±1.75)s,差异有统计学意义(P<0.05)。治疗后,观察组超敏C反应蛋白(hs-CRP)(4.31±1.71)mg/L、白细胞介素-6(IL-6)(24.07±5.03)pg/ml均低于对照组的(6.86±1.59)mg/L、(35.52±4.16)pg/ml,差异有统计学意义(P<0.05)。结论 健脾滋肾汤有助于改善系统性红斑狼疮患者血清炎性因子水平,提高免疫功能及凝血功能,值得推广。

滋肾化瘀汤治疗慢性淋巴细胞白血病临床观察

目的探讨滋肾化瘀汤在慢性淋巴细胞白血病(CLL)患者中的应用效果。方法选取2021年1月—2023年1月山西省中医院收治的106例CLL患者,采用随机数字表法将其均分为2组,各53例。对照组采用常规一线治疗方案,观察组在此基础上增用滋肾化瘀汤,比较2组血清热休克蛋白70(Hsp70)、Th1/Th2与转化生长因子β(TGF-β)、白细胞计数(WBC)、淋巴细胞绝对数(ALC)、主要症状及体征的持续时间、不良反应情况与总有效率。结果观察组总有效率、Hsp70、Th1/Th2均高于对照组(P<0.05);TGF-β,WBC,ALC水平及发热、乏力、疼痛、水肿持续时间均少于对照组(P<0.05);2组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论CLL应用常规化疗方案的同时,增用滋肾化瘀汤可提升疗效,改善症状、外周血象和免疫指标。

滋肾宁心安神汤配合重复经颅磁刺激治疗脑卒中后失眠临床研究

目的:观察滋肾宁心安神汤配合重复经颅磁刺激治疗脑卒中后失眠心肾不交证的临床疗效。方法:选取90例脑卒中后失眠心肾不交证患者,按随机数字表法分为对照组和试验组各45例。对照组剔除4例,纳入41例,予以重复经颅磁刺激治疗。试验组剔除3例,纳入42例,予以滋肾宁心安神汤配合重复经颅磁刺激治疗。2组均治疗4周。比较2组临床疗效、匹兹堡睡眠质量指数(PSQI)评分、中医证候积分、睡眠柏林问卷(BQ)评分、血清褪黑素水平。结果:治疗4周后,试验组总有效率95.24%,高于对照组78.05%(P<0.05)。2组PSQI评分、中医证候积分、BQ评分均较治疗前降低(P<0.05),试验组PSQI评分、中医证候积分、BQ评分均低于对照组(P<0.05)。2组血清褪黑素水平均较治疗前升高(P<0.05),试验组血清褪黑素水平高于对照组(P<0.05)。结论:滋肾宁心安神汤配合重复经颅磁刺激治疗脑卒中后失眠心肾不交证可增强疗效,改善睡眠质量及睡眠呼吸紊乱,缓解临床症状,调节褪黑素水平。

健脾滋肾方抑制系统性红斑狼疮患者的足细胞自噬:基于网络药理学和临床研究

目的 基于网络药理学结合分子对接,通过临床验证,探讨健脾滋肾方从足细胞自噬途径治疗系统性红斑狼疮(SLE)潜在机制。方法 运用TCMSP、GeneCards、OMIM及TTD数据库获取健脾滋肾方及SLE、足细胞自噬相关靶点;取三者交集得到健脾滋肾方经足细胞自噬途径治疗SLE的潜在作用靶点。Cytoscape3.9.1构建“复方-成分-疾病-潜在靶点”网络及蛋白质互作网络,筛选出关键活性成分和靶点,进行分子对接。并临床纳入46例SLE患者和10例健康人,将SLE患者随机分为观察组(n=22)和对照组(n=21)。对照组口服醋酸泼尼松及吗替麦考酚酯,观察组在其基础上加用健脾滋肾方,疗程均为12周。运用ELISA检测SLE组及健康人群尿液中nephrin、synaptopodin水平;使用Western blot检测外周血内p-JAK1/JAK1、pSTAT1/STAT1、LC3II/LC3I、p62蛋白水平,并观察经健脾滋肾方干预后对SLE患者足细胞相关蛋白(nephrin、synaptopodin)、自噬水平(LC3II/LC3I、p62)及p-JAK1/JAK1、p-STAT1/STAT1表达影响。结果 经筛选得到健脾滋肾方经足细胞自噬途径治疗SLE的关键活性成分4种,核心靶点基因5个(STAT1、PIK3CG、MAPK1、PRKCA、CJA1);富集分析显示可能涉及AGERAGE、JAK/STAT、EGFR、PI3K/Akt等信号通路。分子对接结果显示关键活性物质和核心靶点均有较好的结合活性。其中STAT1是结合活性最好的靶蛋白。临床试验证实健脾滋肾方能够显著降低血清中p-JAK1/JAK1及p-STAT1/STAT1、LC3II/LC3I蛋白表达水平(P<0.05或P<0.01),升高p62蛋白表达水平(P<0.05),降低尿液中nephrin、synaptopodin水平(P<0.05)。结论 健脾滋肾方经足细胞自噬治疗SLE具有多成分、多靶点、多通路协同作用的特点,其可能通过槲皮素、山奈酚、β-谷甾醇、异鼠李素等关键活性成分作用于STAT1靶基因,抑制JAK/STAT通路相关基因表达,调控自噬减轻SLE足细胞损伤。

滋肾疏肝方对围绝经期抑郁模型小鼠的作用及机制

目的探讨滋肾疏肝方对围绝经期抑郁(PDD)模型小鼠的作用及其机制。方法采用卵巢切除法和慢性不可预见性刺激建立PDD小鼠模型。48只小鼠随机分为假手术组,模型组,滋肾疏肝方低、中、高浓度组和阳性对照组,每组8只;低、中、高浓度组分别给予0.38、0.76、1.52 g/mL滋肾疏肝方灌胃,阳性对照组给予0.21 g/mL盐酸氟西汀合戊酸雌二醇混悬液灌胃。通过强迫游泳实验、悬尾实验和旷场实验检测PDD小鼠行为学变化;Nissl染色观察PDD小鼠海马神经元的组织学变化;分别采用qRT-PCR及Western blot实验检测各组小鼠海马神经元脑源性神经营养因子(BDNF)、钙调神经磷酸酶(Calcineurin)、cAMP反应元件结合蛋白(CREB)和CREB调节的转录共激活因子1(CRTC1)基因及蛋白表达;ELISA检测各组小鼠海马组织5-羟色胺(5-HT)、多巴胺(DA)和去甲肾上腺素(NE)水平。结果PDD模型小鼠增加强迫游泳实验(FST)和悬尾实验(TST)的不动时间,损伤小鼠海马神经元,抑制BDNF、Calcineurin、CREB和CRTC1的表达,增强盐诱导激酶2(SIK2)和p-TRTC1的表达,降低5-HT、DA和NE的水平;而滋肾疏肝方可逆转PDD建模的影响,尤其以中、高浓度组效果显著。结论滋肾疏肝方可通过CRTC1/CREB/BDNF信号通路,增加单胺类神经递质5-HT、DA、NE的表达,从而修复PDD小鼠海马神经元损伤,发挥抗抑郁作用,为滋肾疏肝方在PDD临床治疗中的应用提供了科学依据,为中医药治疗PDD提供新思路。

滋肾清热利湿化瘀方治疗多囊卵巢综合征的网络药理学作用机制及实验研究

目的采用网络药理学探讨滋肾清热利湿化瘀方(Zishen Qingre Lishi Huayu Prescription,ZQLHP)治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)的作用机制,并进行实验验证。方法基于网络药理学预测滋肾方的核心成分、靶基因和主要通路,对其中PCOS相关成分、靶基因、通路进行筛选;采用来曲唑(letrozole,LET)诱导PCOS小鼠模型,观察滋肾方对PCOS小鼠的作用,并对网络药理学结果进行机制验证。结果网络药理学结果表明,滋肾方456个成分中含有361个相关靶点,PCOS相关靶点1397个,交集靶点125个;获得槲皮素、豆甾醇、β-谷甾醇等主要活性成分与丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)、蛋白激酶1(AKT serine/threonine kinase 1,AKT1)和信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)等核心靶点;GO分析得到BP 663条目,CC 64条目,MF 119条目,其中富集基因数量较多的条目为negative regulation of apoptotic process,plasma membrane,protein binding;KEGG分析显示潜在作用靶点主要富集在癌症信号通路、PI3K-AKT和TNF等信号通路;PPI网络分析结果显示,MAPK3、AKT1和STAT3可能是滋肾方治疗PCOS的关键靶点。动物实验结果表明,与模型组比较,滋肾方组的小鼠的体重降低(P<0.05),且能有效改善PCOS模型小鼠的组织病理学表现,囊性卵泡数量降低(P<0.05),黄体数量增加(P<0.01)。降低卵巢组织中IL-10水平(P<0.01),升高IL-6、TNF-α水平(P<0.05,P<0.01)。Western blot和免疫组织化学(immunohistochemistry,IHC)结果显示,PCOS小鼠卵巢组织p-AKT蛋白表达量下降(P<0.05,P<0.01),p-p38MAPK和p-STAT3蛋白表达较正常组升高(P<0.05,P<0.01),而经滋肾方治疗后p-AKT蛋白表达上升(P<0.05),p-p38MAPK和p-STAT3蛋白表达明显下降(P<0.05,P<0.01)。结论滋肾方可能通过调控AKT/p38MAPK/STAT3信号改善来曲唑诱导的PCOS小鼠的炎性损伤。

滋肾宁心胶囊联合替米沙坦治疗围绝经期高血压临床疗效观察

目的 观察滋肾宁心胶囊联合替米沙坦治疗围绝经期高血压的疗效,及对患者血压、生化指标、中医症状积分的影响。方法 300例围绝经期高血压患者随机分为对照组和观察组各150例。对照组给予替米沙坦治疗,观察组在对照组治疗基础上加用滋肾宁心胶囊,两组疗程均为8周。观察比较两组患者治疗前后24 h动态血压及其变异系数(24 h平均收缩压及其变异系数、24 h平均舒张压及其变异系数)、性激素水平(血清雌二醇、促卵泡生成素、睾酮、孕酮)、血脂(三酰甘油、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇)、肾素和超敏C反应蛋白水平,以及中医症状积分变化,评价两组疗效。结果 治疗后,两组患者的24 h平均收缩压及其变异系数、24 h平均舒张压及其变异系数,性激素、血脂、肾素和超敏C反应蛋白水平,以及中医症状积分等指标均较前明显改善(P <0.05),且观察组各项指标均优于对照组(P <0.05)。观察组治疗总有效率明显高于对照组(P <0.05)。两组不良反应发生率差异无统计学意义(P> 0.05)。结论 滋肾宁心胶囊联合替米沙坦治疗围绝经期高血压临床疗效显著,可有效降低血压、缓解症状,改善性激素、血脂、肾素和超敏C反应蛋白水平。

滋肾育胎丸在卵巢功能下降患者再次冻融胚胎移植中的作用

背景:目前西医对卵巢功能下降患者的主要治疗方法为激素替代治疗,但是这类患者对外源性激素不敏感导致治疗效果不理想。滋肾育胎丸具有养血安胎、补肾健脾、益气培元和强壮身体之功效。有研究证实滋肾育胎丸在降低卵巢功能下降患者促卵泡生成素指标和改善中医症状方面确实有一定的疗效,但是其通过改善内膜容受性提高患者种植率的研究比较少。目的:评价滋肾育胎丸对卵巢功能下降患者再次进行冻融胚胎移植后临床结局的影响。方法:选取2019年1月至2021年12月在常州市妇幼保健院生殖中心首次失败后再次接受冻融胚胎移植助孕的300例卵巢功能下降患者为研究对象,受试者按1∶2的比例随机接受安慰剂或滋肾育胎丸治疗,治疗组100例,对照组200例,但13例患者由于无法联系、拒绝吃药或其他原因而脱落,最终治疗组90例,对照组197例纳入研究。在冻融胚胎移植前7 d开始口服药物,服用剂量为5 g/次,3次/d。研究服用滋肾育胎丸是否能改善卵巢功能下降患者再次冻融胚胎移植后的临床结局,主要结局指标为临床妊娠率、种植率、流产率、活产率以及子代出生体质量和出生缺陷等。结果与结论:与对照组比较,口服滋肾育胎丸后临床妊娠率(P<0.05)和种植率(P=0.009)明显提高;相关性分析显示服用滋肾育胎丸与着床胚胎数呈正相关关系(r=0.200,P=0.001),与临床妊娠呈正相关关系(r=0.235,P=0.000);服用滋肾育胎丸与子宫内膜厚度及血流的各项指标无相关性。提示:滋肾育胎丸可能改善卵巢功能下降患者再次冻融胚胎移植的临床妊娠率和种植率。

滋肾丸对KKay小鼠肝脏胰岛素抵抗以及PI3K-Akt-FOXO1通路的影响

目的 探究不同剂量滋肾丸水提物对于糖尿病小鼠降糖效果及该药对肝脏胰岛素抵抗的作用机制。方法 21只KKay小鼠随机分为模型组、滋肾丸高剂量组和滋肾丸低剂量组,每组7只;7只C57BL/6J小鼠作为正常组。连续灌胃给药6周,滋肾丸高剂量组予2.8 g/(kg·d),滋肾丸低剂量组予1.4 g/(kg·d),模型组、正常组予等体积蒸馏水。观察每周空腹血糖(fasting blood glucose, FBG),最后一周进行口服葡萄糖耐量试验(oral glucose tolerance test, OGTT),酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测各组小鼠血清中的空腹胰岛素(fasting insulin, FINS)并计算胰岛素抵抗指数(homeostasis model assessment-insulin resistance, HOMA-IR),qPCR法检测胰岛素受体底物(insulin receptor substrate, IRS)、磷脂酰肌醇3-激酶(phosphoinositide 3-kinase, PI3K)、蛋白激酶B(protein kinase B,PKB/Akt)、叉头框蛋白1(forkhead box O1,FOXO1)、磷酸烯醇丙酮酸羧激酶(phosphoenolpyruvate carboxykinase, PEPCK)、葡萄糖-6-磷酸酶(glucose-6-phosphatase, G6pase)、葡萄糖激酶(glucokinase, GCK)基因表达水平;苏木素-伊红(hematoxylin-eosin staining, HE)染色和糖原过碘酸雪夫染色(periodic Acid-Schiff staining, PAS)观察肝脏病理情况和糖原分布。结果 与模型组相比,滋肾丸高剂量组和滋肾丸低剂量组小鼠FBG、HOMA-IR、OGTT曲线下面积明显下降,肝脏形态学改变部分减少,脂滴减少,糖原分布增加,FOXO1、PEPCK、G6pase基因表达均明显下降,滋肾丸高剂量组GCK基因表达水平显著上升,差异有统计学意义。结论 滋肾丸对于KKay小鼠降糖效果显著,能明显改善肝脏胰岛素抵抗,其机制可能是降低FOXO1、PEPCK、G6pase的转录水平,提高GCK的转录水平,从而抑制糖异生,促进糖原合成有关。