Bushen Yizhi Formula regulates the IRE1αpathway to alleviate endoplasmic reticulum stress in an Alzheimer’s disease rat model

While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.

The effect of Huayu Lifei formula on the expression of miR-27a and α-SMA in lung tissue of bleomycin-induced rat lung fibrosis model

Objective:Investigating the inhibitory effect of Huayu Lifyei Formula on bleomycininduced rat pulmonary fibrosis and its impact on the expression of miR-27a andα-SMA.Methods:Wistar rats were arbitrarily classified into a normal group,a model group,and a group treated with Huayu Lifyei Formula,each consisting of ten rats.Pulmonary fibrosis rat model was established by injecting bleomycin.Subsequent to the modeling,the Huayu Lifyei Formula treatment group was administered Huayu Lifyei Formula via gavage for a period of 7 days.Rats were sacrificed on the 14th day after modeling.The right lung was taken for HE staining,Masson staining,and immunohistochemical observation of alpha-smooth muscle actin(α-SMA)expression.The expression of miR-27a was measured by qRT-PCR,with the miR-27a binding site on ACTA2(the gene encodingα-SMA protein)confirmed using dualluciferase reporter gene technology.Results:When compared to the model group,the Huayu Lifyei Formula treatment group showed considerable alleviation of pathological morphological changes in lung tissue,with significant reductions in alveolitis,fibrosis,collagen deposition in lung tissue,and the expression ofα-SMA protein.Meanwhile,the expression of miR-27a in the Huayu Lifyei Formula treatment group significantly increased,and the dual-luciferase reporter gene confirmed the binding site of miR-27a with the ACTA2 gene.Conclusion:Huayu Lifyei Formula can inhibit bleomycin-induced pulmonary fibrosis in rats,and its mechanism may be related to the promotion of miR-27a expression.

Antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” and chemotherapy on transplanted animal hepatocarcinoma

AIM: To investigate the antitumor and synergistic effect of Chinese medicine 'Bushen huayu jiedu recipe' (recipe for invigorating the kidney, removing blood stasis and toxic substances) and chemotherapy on mice hepatocarcinoma.METHODS: Bushen huayu jiedu recipe (BSHYJDR)consisting of Chinese Cassia Bark, Psoralea, Zedoary,Rhubarb, etc. is equal to 1.5 g/mL liquid of originated herbs after being decocted, filtered, and concentrated. Kunming mice, weighing 18-22 g, were injected with 0.2 mL ascitic hepatocarcinoma H22 containing 1×107 cells/mL into armpit of the right forelimb of mice. After 24 h, the mice were weighed and randomly divided into tumor-bearing model control group, cisplatin (DDP) group, BSHYJDR high dosage group, low dosage BSHYJDR group, DDP combined with high and low dosage BSHYJDR group, 10 mice in each group. DDP group received injection intraperitoneally (ip) at the dosage of 1 mg/kg (equal to 1/10 LD50), once a day for 4 d. High and low dosage BSHYJDR groups received intragastric BSHYJDR at the dosages of 26.6 and 13.3 g/kg (20 and 10 times each of clinical adult dosage)respectively, while tumor-bearing model group received the equal volume of distilled water once a day for 10 d. On the 11th d, the mice were weighed and killed, then the tumor was dissected and weighed, the repression rate (RR) was calculated according to the mean weight of tumor (MWT).RESULTS: Compared to the model group (MWT: 1.30±0.73),DDP group (MWT: 0.41+0.09, RR: 68.46%) had a significant difference in the inhibition of hepatocarcinoma H22 (P＜0.01).High dosage BSHYJDR group (MWT: 0.69+0.29, RR:46.92%) also had a significant difference in inhibition (P＜0.05), while no difference was found in low dosage BSHYJDR group (MWT: 0.85+0.34, RR: 34.62%) (P＞0.05).When DDP was combined with high dosage BSHYJDR (MWT: 0.29±0.17, RR: 77.69%) and low dosage BSHYJDR (MWT: 0.38±0.21, RR: 70.77%) respectively, we could see improvement of the inhibition effect of DDP on transplanted hepatocarcinoma H22. DDP combined with high dosage BSHYJDR had a significant difference (P＜0.001) compared to DDP, while DDP combined with low dosage BSHYJDR only had a little improvement that is not remarkable.CONCLUSION: Chinese medicine BSHYJDR in combination with chemotherapy can inhibit transplanted hepatocarcinoma in mice.

Intervention of Bushen Yizhi formula on cognitive disorder rat and the related mechanism of the protective function on neural network

OBJECTIVE Bushen Yizhi formula,constructed by Prof LIAO Shi-long′research group(Guangzhou University of chinese medicine),is the combination of clinical experience and modern pharmacological research,and mainly focuses on the etiology and pathogenesis of AD for treating both cause and symptoms.In this research,the pharmacodynamic study protocol of Bushen Yizhi formula was designed according to the characteristics and indications function of herbs in the formula,and was conformed to preclinical pharmacological research of traditional Chinese medicine for AD,The Technical Requirements of Pharmacology and Toxicology Research in New Drug Development Enacted by State Food and Drug administration also was guiding principle.METHODS A preliminary randomized double-blind clinical trail with 141 cases of AD showed that the efficiency of Bushen Yizhi formula was 61.9%and the increased mean of MMSE was 3.17,but the specific mechanism remains unclear.This study was aimed to reveal the preventive and therapeutic effect of Bushen Yizhi formula on AD rats and its related mechanism.In this research,forebrain-injected IBO-induced AD rats(cholinergic neuron lesion),senescence accelerated mouse,scopolamineinduced learning and memory deficiency rats(mild cognitive impairment)were all established.The learning and memory ability was tested with Morris water maze.Then formation of age pigment,extent of neuronal loss,activation of astrocytes,content of NTFs and degree of oxidized stress damage were determined by morphology,mmunohistochemical and molecular biology methods.RESULTS As the application of Bushen Yizhi formula,the learning and memory ability in all three groups were significantly improved,the formation of age pigment and the content of ACH in cortex and hippocampus were reduced,the activation of astrocytes and release of inflammatory factor(TNF-αand IL-1β)were inhibited,and the antioxidases(CAT,SOD,GSH-PX)were up-regulated and MDA was down-regulated.CONCLUSION Bushen Yizhi formula can prevent and treat AD rats,which might be achieved by anti-inflammatory,antioxidant and protecting cholinergic neuron.

Mechanism of treating recurrent abortion with “Peiyuan Bushen Antai formula” based on network pharmacology and molecular docking

Objective:To study the effective compound action target signal pathway of Peiyuan bushenan taifang(PYBSATF)has achieved good clinical efficacy in the treatment of recurrent spontaneous abortion(RSA),but its mechanism has not been clarified because of its complex components.In this study,network pharmacology is applied to study the effective compounds,targets and signal pathways of PYBSATF in the treatment of RSA,so as to reveal its pharmacological mechanism of action in the treatment of recurrent spontaneous abortion.Methods:The Traditional Chinese Medicine Systems Pharmacology database(TCMSP)and CNKI are used to obtain the main compounds and drug action targets of PYBSATF.Genecards and the Online Mendelian Inheritance of Man databases(OMIM)are searched to collect the known genes related to RSA,so as to construct compound-target network and screen out the common target proteins and main active compounds.We also use string database to construct a visual protein-protein interaction network(PPI).Cluster Profiler and R software were used to analyze the common targets of drugs and diseases for GO function analysis and KEGG pathway enrichment analysis.Finally,the compound and the protein sequences were conducted according to the node parameters,so that the core protein and core compounds are used to perform molecular docking.Results:186 potential active components and 65 predicted action targets of PYBSATF were screened out.At the same time,1658 genes were also screened out to be closely related to RSA,among which 65genes overlaped with PYBSATF targets and were considered to be related to way of treatment.PPI network showed that VEGFA,IL6,EGFR,MAPK8 and ESR1were the core targets of PYBSATF for the treatment of RSA.GO and KEGG enrichment analysis obtained 93 biological processes of cells(P<0.01)and 87 signaling pathways(P<0.01).PYBSATF played a pharmacological role through a variety of pathways including anti-inflammatory,anti-apoptosis,promoting proliferation and angiogenesis.Molecular docking showed that most active components and key targets of PYBSATF had strong efficiency.Conclusion:Through the study of network pharmacology,it predicted that PYBSATF might treat RSA through multiple targets and multiple signal pathways.Significantly,the predictive targets may be potential targets for treatment of RSA.

Expression of Nrf2/ARE pathway in diabetic nephropathy and renal protection of Qihuang Bushen Xiezhuo Formula

Objective:To investigate the effect of Qihuang Bushen Xiezhuo Formula on the expression of the nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway of human glomerular mesangial cells(HMC)in high glucose medium and its protective effect on oxidative stress.Methods:The HMC were cultured in vitro to prepare normal rat serum.The rats were intragastrically administered with irbesartan and Qihuang Bushen Xiezhuo Formula.The serum containing the drugs was prepared after the blood concentration was reached.The rats were divided into the control group,the high glucose group,the irbesartan group and the Qihuang Bushen Xiezhuo Formula group.The HMC of the control group was cultured with normal rat serum(10%serum concentration)medium,while that of the high glucose group was cultured with high glucose medium of rat serum(10%serum concentration).The irbesartan group and the Qihuang Bushen Xiezhuo Formula group were respectively treated with 10%irbesartan and 10%Qihuang Bushen Xiezhuo Formula in serum high glucose medium.After 48 h of culture,the relevant indicators were collected and detected.The mRNA expression levels of Nrf2,gamma-glutamylcysteine synthetase(γ-GCS)and superoxide dismutase(SOD)in each group were detected by real-time PCR.The expressions ofγ-GCS and SOD were detected by immunohistochemistry.The protein expressions ofγ-GCS and SOD in HMC of each group were observed by Western Blot.Results:The expressions of Nrf2,γ-GCS,SOD mRNA and protein in experimental cells of each group were low in the control group,while those in the high glucose group were decreased as compared with the control group(P<0.05).After interference of irbesartan and Qihuang Bushen Xiezhuo Formula the expressions were increased,and the increase in Qihuang Bushen Xiezhuo Formula group was more significant(P<0.05).Conclusion:Qihuang Bushen Xiezhuo Formula can improve HMC oxidative stress injury in high glucose culture,and its mechanism may be achieved by activating Nrf2 and its related downstream proteinsγ-GCS and SOD.

补肾活血方对抗磷脂抗体阳性复发性流产患者外周血microRNA-423-5p表达的影响及疗效分析

目的 探讨抗磷脂抗体阳性复发性流产(RSA)患者外周血miR-423-5p表达及补肾活血方的干预效果。方法 选取2017年5月—2019年12月河南大学淮河医院收治的92例抗磷脂抗体阳性RSA患者。将患者分为对照组和研究组,每组46例。对照组给予常规西医治疗,研究组在对照组基础上另给予补肾活血方干预,两组均持续治疗8周,并自治疗起始随访2年。对比两组患者治疗前后中医证候评分、血管生成因子及蜕膜化标志因子变化情况,统计两组患者治疗前后miR-423-5p表达及凝血功能变化情况,记录两组患者治疗期间药物安全性,统计两组患者随访期间妊娠及成功分娩情况。结果 研究组治疗前后的主证、次证中医证候评分的差值高于对照组(P <0.05)。研究组治疗前后的转化生长因子β1、血管内皮生长因子、胰岛素样生长因子结合蛋白1、miR-423-5p、凝血酶原时间、活化部分凝血活酶时间、凝血酶时间、D-二聚体的差值高于对照组(P <0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。两组患者妊娠率比较,差异无统计学意义(P>0.05)。研究组活产率高于对照组(P <0.05)。结论 补肾活血方干预可减轻抗磷脂抗体阳性RSA患者病情,改善血管生成因子、蜕膜化标志因子、凝血功能,抑制miR-423-5p表达也较明显,可提升活产率,且安全性良好。

补肾化瘀方加减对肾虚血瘀型子宫内膜异位症术后复发的预防作用与机制研究

[目的]探讨补肾化瘀方加减对肾虚血瘀型子宫内膜异位症术后复发的预防作用与机制。[方法]选择于2019年1月—2021年1月在衡水市第四人民医院治疗的子宫内膜异位症患者320例,按随机数字表法随机分组,常规西医组160例,给予患者常规西医治疗,补肾化瘀方组160例,在常规西医治疗同时给予患者补肾化瘀方加减治疗,治疗前后检测两组患者血清性激素[促黄体生成素(LH)、孕激素(P)、雌激素(E2)],肿瘤坏死因子-α(TNF-α),血管内皮生长因子(VEGF),抗子宫内膜抗体(EMAb)水平,通过语言描述评分法(VRS)评价患者痛经及非经期盆腔痛情况,给予患者中医证候评分,比较两组临床疗效,记录两组患者2年复发率及治疗期间两组患者不良反应发生情况。[结果]补肾化瘀方组患者痛经及非经期盆腔痛评分低于常规西医组(P<0.05),补肾化瘀方组TNF-α、VEGF、EMAb水平较常规西医组低(P<0.05),补肾化瘀方组患者LH、P、E2含量较常规西医组明显低(P<0.05),补肾化瘀方组患者中医证候评分较常规西医组明显降低(P<0.05),补肾化瘀方组患者总有效率(97.50%)较常规西医组(88.13%)高(P<0.05),常规西医组2年复发率为12.90%,补肾化瘀方组2年复发率为3.21%,两组2年复发率比较,差异有统计学意义(P<0.05),补肾化瘀方组开始复发时间长于常规西医组(P<0.05);治疗期间两组患者均无明显不良反应发生。[结论]补肾化瘀方加减治疗肾虚血瘀型子宫内膜异位症术后疗效显著,可有效缓解患者痛经及非经期盆腔痛,降低复发率,其作用机制可能与其抑制机体炎症,降低VEGF、EMAb水平,改善性激素水平有关。

补肾活血膏方对肾虚血瘀证强直性脊柱炎患者的临床疗效

目的 探讨补肾活血膏方对肾虚血瘀证强直性脊柱炎患者的临床疗效。方法 167例患者随机分为对照组(常规治疗,55例)、暴露组(常规治疗+补肾活血汤剂,54例)、高暴露组(常规治疗+补肾活血汤剂+补肾活血膏方,58例),疗程2年。检测临床疗效、BASDAI评分、ASDAS-CRP、BASFI评分、脊柱痛评分、PGA评分、BASMI评分、ASQoL评分、SPARCC评分、肾虚血瘀证评分、ESR、CRP、IL-6、TNF-α、IL-17、IL-23、IL-35、NLR、PLR、安全性指标变化。结果 高暴露组ASAS40、ASAS5/6、BASDAI50例数多于暴露组和对照组(P<0.05)。治疗后,高暴露组BASDAI评分、ASDAS-CRP、BASFI评分、脊柱痛评分、PGA评分、BASMI评分、SPARCC评分、ASQoL评分、肾虚血瘀证评分、ESR、CRP、IL-6、TNF-α、IL-17、IL-23低于其他2组(P<0.05),IL-35更高(P<0.05)。经Logistic回归分析校正混杂因素后,补肾活血汤、补肾活血膏方降低BASDAI评分和ASDAS-CRP(P<0.05),提高临床疗效(P<0.05)。3组未发现严重不良反应。结论 补肾活血膏方可安全有效地抑制肾虚血瘀证强直性脊柱炎患者炎症,降低疾病活动度,减轻骨髓水肿,改善临床症状,提高关节功能和生活质量。

基于EETs介导的细胞焦亡探讨化瘀祛痰方对ApoE^(-/-)小鼠动脉粥样硬化的影响

目的 探讨化瘀祛痰方对ApoE-/-小鼠动脉粥样硬化(AS)的影响及机制。方法 将30只ApoE-/-小鼠随机分为模型组、化瘀祛痰方组[20 g/(kg·d)]和瑞舒伐他汀组[1.55 mg/(kg·d)],每组10只,另取10只C57BL/6J小鼠作为正常对照组。ApoE-/-小鼠喂饲高脂饲料12周复制AS模型。造模成功后,各组小鼠灌胃相应药物或生理盐水,每日1次,连续4周。末次给药后,检测各组小鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、5,6-环氧二十碳三烯酸(5,6-EET)、8,9-EET、11,12-EET、14,15-EET、白细胞介素1β(IL-1β)、IL-18水平,主动脉组织中核因子κB抑制蛋白(IκB)、核因子κB(NF-κB)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶1(Caspase-1)、IL-1β、IL-18 mRNA表达水平和IκB、NF-κB、NLRP3、凋亡相关斑点样蛋白质(ASC)、Caspase-1、消皮素D(GSDMD)、IL-1β、IL-18蛋白表达水平,并观察主动脉组织形态学变化。结果 与模型组比较,化瘀祛痰方组及瑞舒伐他汀组小鼠血清中TC、TG、LDL-C、IL-1β、IL-18水平,主动脉组织中IκB、NF-κB、NLRP3、Caspase-1、IL-1β、IL-18 mRNA表达水平以及IκB、NF-κB、NLRP3、ASC、Caspase-1、GSDMD、IL-1β、IL-18蛋白表达水平均显著降低(P<0.05),血清中5,6-EET、8,9-EET、11,12-EET、14,15-EET水平均显著升高(P<0.05);主动脉粥样斑块明显减少。结论 化瘀祛痰方可能通过EETs介导细胞焦亡发挥抗AS作用。

基于JAK/STAT3通路探讨补肾活血方改善单侧输尿管梗阻大鼠炎症和肾纤维化

目的:观察补肾活血方(BSHXF)对单侧输尿管梗阻大鼠(unilateral ureteral obstruction,UUO)肾纤维化和炎症的治疗效果,揭示其抗炎及延缓肾纤维化的机制。方法:32只8周龄雌性SD大鼠根据随机数字表分为假手术组(Sham组)、单侧输尿管梗阻组(UUO组)、补肾活血方低剂量组(BSHXF-L组)和补肾活血方高剂量组(BSHXF-H组)。造模后第2天开始,连续灌胃干预21 d,BSHXF-L组和BSHXF-H组给予相应剂量补肾活血方汤剂,Sham组和UUO组给予与BSHXF组等体积的生理盐水。干预结束后,记录24 h尿量,全自动生化分析仪检测血肌酐、尿素氮、尿蛋白、尿肌酐和肾功能指数;采用HE和Masson染色检测肾脏病理损伤和纤维化程度;通过免疫组化染色分析各组TGF-β和TNF-α;Western blotting检测各组TGF-β_(1)、α-SMA、JAK、STAT3、p-STAT3、TNF-α、Caspase-3和Bax的蛋白表达情况。结果:与UUO模型组相比,BSHXF-L组和BSHXF-H组能明显明显改善UUO大鼠的肾功能,降低大鼠肾组织中TGF-β_(1)和α-SMA蛋白表达水平,抑制JAK、STAT3和p-STAT3表达,减少炎症细胞浸润和纤维组织以及胶原的增生,显著降低大鼠的肾脏指数和TNF-α等炎症指标。结论:补肾活血方可通过抑制JAK/STAT3通路激活,改善UUO大鼠肾功能,减轻其肾脏炎症水平、肾脏指数,延缓肾纤维化进程。

补肾益冲方对卵巢储备功能减退大鼠卵巢组织形态及性激素的影响

目的:研究补肾益冲方对卵巢储备功能减退(DOR)模型大鼠卵巢功能的影响。方法:选取雌性未孕SD大鼠40只,随机分为空白组、模型组、补肾益冲方组、补佳乐组。除空白组外,其余大鼠采用雷公藤多苷片混悬液灌胃制备DOR大鼠模型,造模成功后分别给予补肾益冲方及补佳乐进行相应的治疗干预。药物干预结束后,采用酶联免疫吸附试验法(ELISA)检测大鼠血清中抗苗勒管激素(AMH)、促卵泡生成素(FSH)、雌二醇(E_(2))、促黄体生成素(LH)的水平;HE染色观察大鼠卵巢组织的病理学形态变化。结果:与空白组比较,模型组大鼠血清FSH和LH水平升高(P<0.05),AMH和E_(2)水平降低(P<0.05);卵巢中原始卵泡和生长卵泡的数量减少,闭锁卵泡增加;卵巢间质增生并纤维化。补肾益冲方干预后,DOR大鼠血清中FSH和LH激素水平降低(P<0.05),AMH和E_(2)激素水平升高(P<0.05);卵巢组织形态得到改善,原始卵泡和生长卵泡增多,闭锁卵泡减少。结论:补肾益冲方对DOR大鼠卵巢组织形态、卵母细胞的数量和质量具有改善作用,能调节AMH、FSH、E_(2)和LH从而提高DOR大鼠的卵巢储备功能。

补肾健脾方治疗卵巢储备功能减退相关不孕脾肾两虚证临床观察

目的:研究补肾健脾方治疗卵巢储备功能减退相关不孕脾肾两虚证的临床疗效。方法:纳入60例卵巢储备功能减退相关不孕脾肾两虚证患者,采用随机数字法分成治疗组和对照组,每组30例。治疗组患者给予补肾健脾方治疗,对照组患者给予芬吗通治疗,两组均连续治疗6个周期。检测性激素指标[基础卵泡刺激素(bFSH)、基础黄体生成素(bLH)、血清雌二醇(E2)、抗米勒管激素(AMH)]、超声指标[卵巢体积、窦卵泡(AFC)数量],比较两组患者中医证候积分、总有效率、妊娠率、流产率,并监测安全性指标。结果:治疗组总有效率为79.31%(23/29),对照组总有效率为82.14%(23/28),差异无统计学意义(P>0.05)。经过6个月经周期治疗后,两组治疗后中医证候积分、bFSH均较治疗前下降(P<0.05),AMH较治疗前升高(P<0.05),且治疗组优于对照组(P<0.05)。治疗组治疗后bLH较治疗前下降(P<0.05);对照组治疗前后bLH比较,差异无统计学意义(P>0.05)。两组治疗后E2较治疗前有明显升高(P<0.05),两组患者治疗后E2比较,差异无统计学意义(P>0.05)。治疗组治疗后卵巢体积明显增大(P<0.05),窦卵数量明显增多(P<0.05),治疗组明显优于对照组(P<0.05)。治疗组妊娠率[34.48%(10/29)]高于对照组[21.43%(6/28)](P<0.05),治疗组流产率[10.00%(1/10)]低于对照组[33.30%(2/6)(P<0.05)]。两组患者治疗前后安全性指标未发现异常,未发生不良反应。结论:补肾健脾方能安全有效地治疗卵巢储备功能减退相关不孕脾肾两虚证,改善卵巢相关激素水平,提高妊娠率,降低流产率,缓解临床症状。

补肾运脾方联合生长激素治疗脾肾不足型生长激素缺乏症患儿的临床效果

目的 探讨补肾运脾方联合生长激素治疗脾肾不足型生长激素缺乏症患儿的临床效果。方法 选取2021年9月至2023年3月仪征市中医院收治的100例脾肾不足型生长激素缺乏症患儿,按照随机数字表法分为对照组(n=50)与观察组(n=50)。对照组采用生长激素治疗,观察组采用补肾运脾方联合生长激素治疗。比较两组临床疗效、生长发育情况和代谢指标。结果 观察组总有效率高于对照组(P <0.05)。治疗后,观察组生长发育情况优于对照组(P<0.05)。治疗后,观察组生长激素、胰岛素样生长因子-1水平均高于对照组(P<0.05)。结论 补肾运脾方联合生长激素治疗脾肾不足型生长激素缺乏症患儿的临床效果较好,可促进患儿生长发育,改善代谢指标,值得临床推广。

补肾中药复方对高盐摄入去卵巢大鼠骨代谢及ENaCα、NCC和ClC-3表达的影响

目的:探讨补肾中药复方(Bushen formulae,BHF)对高盐摄入去卵巢大鼠骨代谢的影响及其可能的作用机制。方法:80只SPF级SD雌性大鼠按随机数字表法分为假手术组、模型组、中高盐组、高盐组、补肾方组、补肾方+生理盐水组、补肾方+中高盐组、补肾方+高盐组,每组各10只,造模后给予不同饮食、补肾中药复方干预,中高盐饮食、高盐饮食中氯化钠添加浓度分别为2%w/w、8%w/w,补肾中药复方干预剂量为7.8 g·kg^(-1)·d^(-1),每日1次,连续给药12周。检测各组骨密度、骨微结构、骨参数、骨代谢生物标志物、骨组织病理变化情况以及采用Western blot检测骨组织上皮钠离子通道α(ENaCα)、钠-氯同向转运体(NCC)、电压门控性氯离子通道3(ClC-3)蛋白的表达。结果:与假手术组相比,模型组大鼠骨密度降低,骨微结构破坏;与模型组相比,中高盐、高盐饮食组大鼠骨微结构破坏更为明显,同时高盐组骨形成标志物骨钙素(BGP)、Ⅰ型原胶原氨基端前肽(PINP)水平显著上升(P<0.05),骨吸收标志物Ⅰ型胶原氨基端肽(NTX)、Ⅰ型胶原羧基端肽(CTX)、抗酒石酸酸性磷酸酶(TRACP)均显著增加(P<0.05),骨代谢处于高转换状态;高盐饮食加速骨小梁结构的破坏,Western blot结果显示高盐饮食引起股骨组织ENaCα、ClC-3蛋白表达水平下降(P<0.05),NCC蛋白表达水平升高(P<0.05),补肾中药复方干预后能够不同程度的调节高盐引起的相关离子通道的表达。结论:补肾中药复方能够不同程度的调节高盐引起的相关离子通道ENaCα、ClC-3、NCC的表达,对骨代谢失衡具有一定的改善和治疗作用。

穴位埋线联合涤浊化瘀方治疗肥胖型非酒精性脂肪性肝病的疗效观察

目的:观察穴位埋线联合涤浊化瘀方治疗肥胖型非酒精性脂肪性肝病(NAFLD)的临床疗效。方法:选取84例肥胖型NAFLD患者作为研究对象,按随机数字表法分为治疗组和对照组,每组42例,两组患者均给予涤浊化瘀方和健康宣教,治疗组患者在此基础上采取穴位埋线治疗,每2周1次,疗程12周。比较两组患者治疗前后体质量指数(BMI)、腰围、体质量、血脂水平、肝功能、受控衰减参数(CAP)值和中医证候积分的变化情况。结果:治疗组患者治疗后BMI、腰围、体质量、CAP值明显低于治疗前(P<0.05),两组患者治疗后BMI、腰围、CAP值均明显下降,治疗组下降更明显(P<0.05);两组患者治疗后甘油三酯(TG)、总胆固醇(TC)水平明显低于治疗前(P<0.05);治疗组患者治疗后丙氨酸氨基转移酶(ALT)、γ谷胺酰转肽酶(GGT)水平明显低于治疗前,对照组患者治疗后GGT水平明显低于治疗前(P<0.05);两组患者治疗后中医证候积分均明显改善,治疗组患者在改善胁痛、痰多口黏、大便黏腻方面优于对照组(P<0.05);治疗组总有效率97.6%,对照组总有效率88.1%,差异有统计学意义(P<0.05)。结论:对肥胖型NAFLD患者采用穴位埋线联合涤浊化瘀方治疗可有效提高临床疗效,明显改善患者临床症状,降低BMI、腰围、体重、血脂、肝功能、CAP值等指标。

补肾化痰方含药血清对HepG2肝癌细胞增殖、迁移的实验研究

目的:研究补肾化痰方(BHF)对小鼠脏器指数及BHF含药血清对HepG2肝癌细胞增殖、迁移的影响。方法:将小鼠随机分为对照组、BHF高剂量组、BHF中剂量组、BHF低剂量组,灌胃7 d后,采血制备含药血清,处死后取材测定各组小鼠脏器指数。体外培养HepG2肝癌细胞,设置空白组、对照组、BHF高剂量组、BHF中剂量组、BHF低剂量组,每组设3个浓度(20%、10%、5%),3个复孔。各组加入相应的含药血清,培养24、48、72 h后,采用CCK8法测算细胞增殖抑制率。采用Transwell细胞培养24 h后镜下观察各组细胞的形态学改变。进行细胞划痕实验,检测各组HepG2细胞迁移的水平。结果:在20%血清浓度下,与对照组比较,24 h时BHF高、低剂量组细胞增殖抑制率显著增加(P<0.05)。72 h时BHF各剂量组细胞增殖抑制率均显著增加(P<0.05),且高、低剂量组均高于中剂量组(P<0.05)。在10%血清浓度下,与对照组比较,24 h时BHF低剂量组细胞增殖抑制率显著增加(P<0.05),72 h时BHF各剂量组细胞增殖抑制率均显著增加(P<0.05),且高剂量组显著高于低剂量组(P<0.05)。在5%血清浓度下,与对照组比较,48 h时BHF高剂量组显著增加(P<0.05)。72 h时BHF各剂量组细胞增殖抑制率均显著增加(P<0.05),且高剂量组显著高于中、低剂量组(P<0.05)。与空白组比较,72 h时BHF高剂量组划痕迁移率显著降低(P<0.05)。结论:BHF含药血清对HepG2肝癌细胞增殖、迁移具有抑制作用,且高剂量组表现最优。

补肾健脾通络方结合五行健骨操对老年骨质疏松脾肾两虚证患者骨密度、骨代谢及炎症水平的影响

目的:观察补肾健脾通络方结合五行健骨操对老年骨质疏松脾肾两虚证患者骨密度、骨代谢及炎症水平的影响。方法:选取100例老年骨质疏松脾肾两虚证患者,采用简单随机法分为两组。西药组给予碳酸钙D_(3)联合骨化三醇治疗,综合组在西药组基础上给予补肾健脾通络方结合五行健骨操干预。比较两组治疗前后动态平衡、骨密度、骨代谢、炎症水平及中医症候积分差异,统计不良反应。结果:综合组治疗后睁眼和闭眼的动态平衡参数低于西药组(均P<0.05)。综合组股骨颈和腰椎骨密度(BMD)及骨钙素(BGP)、总Ⅰ型前胶原氨基端前肽(T-PINP)、25-(OH)D_(3)治疗后较治疗前升高,综合组治疗后高于西药组(均P<0.05)。综合组C反应蛋白(CRP)、β-胶原特殊序列(β-CTX)、巨噬细胞集落刺激因子(M-CSF)、肿瘤坏死因子-α(TNF-α)治疗后较治疗前降低,综合组治疗后低于西药组(均P<0.05)。综合组中医症候积分治疗后较治疗前降低,综合组治疗后低于西药组(均P<0.05)。两组不良反应比较,差异无统计学意义(P>0.05)。结论:补肾健脾通络方结合五行健骨操可减轻老年骨质疏松脾肾两虚证患者炎症反应,改善骨密度和骨代谢,提高平衡功能。

基于网络药理学研究培元化瘀解毒方治疗胃癌的作用机制

目的探讨培元化瘀解毒方治疗胃癌的网络药理学作用机制。方法利用中医药数据库和文献检索筛选培元化瘀解毒方的生物活性成分,预测其作用靶点,从疾病数据库检索胃癌相关靶点,构建药效分子-靶点网络及蛋白质-蛋白质相互作用(PPI)网络,然后进行KEGG分析、GO富集分析。结果检索获得培元化瘀解毒方中药的有效活性成分206种,药效分子靶点基因211个,有对应靶点信息的有效成分132个,对应关系1131个;检索得到胃癌靶点184个;通过PPI对药物靶点进行扩增得到3592个直接或间接靶点,与疾病靶点取交集得到144个靶点。PPI分析表明,排名靠前的靶点与胃癌密切相关,富集分析也显示这些靶点在癌症通路中被富集。结论本研究初步揭示了培元化瘀解毒方在胃癌治疗中的有效成分、潜在靶点及可能的作用机制,为中西医结合治疗胃癌提供参考。

补肾养血调经方治疗肾虚血瘀型PCOS的真实世界研究

目的观察补肾养血调经方治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)的真实世界临床疗效。方法收集2019年9月至2021年9月在河南中医药大学第一附属医院,142例经补肾养血调经方治疗的PCOS患者临床资料,根据有无生育需求及不孕情况,将142例PCOS患者分为3组。A组:无生育需求的PCOS患者;B组:有生育需求非不孕症的PCOS患者;C组:合并不孕症的PCOS患者。对3组患者治疗前后月经、妊娠、分娩及新生儿体质量等情况进行随访。结果116例PCOS患者月经情况得到不同程度的改善,临床有效率达81.69%。A组无生育需求的94例PCOS患者中,生化妊娠5例(5.32%),临床妊娠5例(5.32%),持续妊娠5例(5.32%),活产4例,妊娠状态1例;B组有生育需求的29例非不孕症患者中,生化妊娠8例(27.59%),临床妊娠7例(24.14%),持续妊娠6例(20.69%),活产6例(20.69%);C组PCOS合并不孕症者19例,平均不孕病程为(2.36±1.47)年,经治疗,生化妊娠7例(36.84%),异位妊娠1例(14.29%),临床妊娠6例(31.58%),早期流产1例(16.67%),持续妊娠5例(26.32%),晚期流产1例(16.67%),活产2例,妊娠状态2例。3组患者生化妊娠率、临床妊娠率、持续妊娠率进行组间比较,差异具有统计学意义(P<0.05)。所有妊娠患者中妊娠期糖尿病者3例(15.00%),妊娠期高血压者1例(5.00%),妊娠期亚临床甲状腺功能减退者2例(10.00%)。患者均为足月产,新生儿中巨大儿1例,余体质量均在正常范围,随访子代身体状况均良好。治疗期间患者均未出现严重不良反应。结论补肾养血调经方可明显改善PCOS患者月经情况及生殖结局,安全性好。