Ethnopharmacological relevance: Chaihu-Shugan-San (CSS) is a classic traditional Chinese medicine (TCM) formula from the Ming Dynasty "Jingyue's Complete Works". In China, it is prevalent for the treatment of a wide range of ailments, with a particular emphasis on functional gastrointestinal disorders (FGIDs). Clinical evidence suggests that CSS has been found to be a highly effective therapeutic approach for the treatment of Functional Dyspepsia (FD), however, there is a limited amount of high-quality clinical evidence, particularly randomized, double-blind, placebo-controlled trials to support this claim. Aim of the study: To evaluate the therapeutic efficacy of Chaihu-Shugan-San (CSS) for treating functional dyspepsia (FD) by comparing it to placebos, as well as to investigate the impact of CSS on the gut microbiota in individuals diagnosed with FD. Materials and methods: This was a randomized double-blind, placebo-controlled clinical trial implemented at Shuguang Hospital in Shanghai. Between May 2021 and December 2022, 94 participants satisfying the Rome IV diagnostic criteria for FD were enrolled. They were assigned randomly to either the CSS group or the placebo group, with an equal allocation ratio of 1:1. Patients in both groups received the intervention for four weeks. The primary outcome was the dyspepsia symptom scores evaluated by using single dyspepsia symptom scale (SDS) after four weeks of treatment. The secondary outcomes were the solid gastric empties rate measured by a barium strip method, Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), and Functional dyspepsia Quality of life scale (FDDQL). In addition, after unblinding, 30 patients in the CSS group were randomly selected and divided into before and after treatment of the FD groups (FD1, FD2), and 30 healthy participants were selected as healthy control group (HC), and the gut microbiota was analyzed by 16S rRNA sequencing. Results: After four weeks of treatment, the SDS score exhibited a significant improvement in the CSS group compared to the placebo group (t = 4.882; P < 0.001). The difference in barium strip gastric emptying rate in the CSS group showed a significant ascent compared to the control group (P < 0.01). The HAMA, HAMD, and FDDQL scores in the CSS group showed a statistically significant increase compared to the control group (all P < 0.01). The results of 16S rRNA sequencing revealed that FD patients had less diverse and abundant microbiota than the healthy people. Additionally, the application of CSS resulted in the modulation of certain bacterial populations, leading to both up-regulation and down-regulation of their quantities. Conclusions: These findings suggested that CSS is more effective compared to a placebo in treating FD, relieves anxiety and depression, increases gastric emptying rate in FD patients, and that CSS also affects the bacterial community structure in FD patients.

功能性消化不良是以消化不良为主要症状但并无器质性病变的临床常见疾患,是中医治疗的优势病种.本文通过对近年来中医药治疗功能性消化不良的实验及临床研究文献进行整理,分别从促进胃肠动力、调节脑肠肽、降低内脏高敏感、调节肠道菌群等机制及临床应用方面进行综述,为后续深入研究及临床应用提供参考.

目的 基于氧化应激及腺苷一磷酸(AMP)活化蛋白激酶(AMPK)/沉默信息调节因子3(SIRT3)信号通路探讨柴胡疏肝散干预功能性消化不良(FD)大鼠的作用机制.方法 将32只SD大鼠随机分为正常组、模型组、柴胡疏肝散组、多潘立酮组,每组8只.模型组、柴胡疏肝散组、多潘立酮组均用改良夹尾刺激法造模,造模的同时正常组和模型组予质量分数为0.9%的氯化钠溶液灌胃,柴胡疏肝散组和多潘立酮组分别予柴胡疏肝散水煎液(4.8 g/kg)、多潘立酮混悬液(4.5 mg/kg)灌胃,连续干预4周.干预结束后,检测大鼠胃排空率,苏木精-伊红(HE)染色法观察胃组织病理变化,透射电镜观察胃Cajal间质细胞(ICCs)线粒体超微结构,酶联免疫吸附试验(ELISA)法检测大鼠血清活性氧(ROS)、丙二醛(MDA)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平,实时荧光定量逆转录聚合酶链式反应(RT-qPCR)法检测大鼠胃组织AMPK、SIRT3、锰超氧化物歧化酶(MnSOD)mRNA表达水平,Western blot法检测大鼠胃组织磷酸化AMPK(p-AMPK)、AMPK、SIRT3、MnSOD、微管相关蛋白轻链3(LC3)、P62蛋白表达.结果 ①与正常组比较,模型组大鼠胃排空率降低(P<0.05),ICCs线粒体肿胀、形态欠规则,分支较多,呈空泡化改变,见自噬小体;与模型组比较,柴胡疏肝散组、多潘立酮组大鼠胃排空率升高(P<0.05),ICCs线粒体结构损伤减轻.②与正常组比较,模型组大鼠血清ROS、MDA水平升高(P<0.05),SOD、CAT、GSH-Px水平降低(P<0.05);与模型组比较,柴胡疏肝散组、多潘立酮组大鼠血清ROS、MDA水平降低(P<0.05),SOD、CAT、GSH-Px水平升高(P<0.05).③与正常组比较,模型组大鼠胃组织AMPK、SIRT3、MnSOD mRNA表达水平降低(P<0.05);与模型组比较,柴胡疏肝散组、多潘立酮组大鼠胃组织AMPK、SIRT3、MnSOD mRNA表达水平升高(P<0.05).④与正常组比较,模型组大鼠胃组织LC3Ⅱ蛋白表达水平升高(P<0.05),SIRT3、MnSOD、P62蛋白表达水平及p-AMPK/AMPK值降低(P<0.05);与模型组比较,柴胡疏肝散组、多潘立酮组大鼠胃组织LC3Ⅱ蛋白表达水平降低(P<0.05),SIRT3、MnSOD、P62蛋白表达水平及p-AMPK/AMPK值升高(P<0.05).结论 柴胡疏肝散可有效促进FD大鼠胃动力,其作用与激活AMPK/SIRT3通路、减轻线粒体氧化应激、抑制ICCs自噬有关.

功能性胃肠病是临床常见的一组证候群疾病,症状重叠、病程迁延,严重影响患者的生活质量.其发病机制较为复杂,治疗效果欠佳,常规治疗超过12周效果不理想者,可称为难治性功能性胃肠病.乌梅丸是《伤寒论》中厥阴病的主方,能养肝阴、疏肝用,清上热、温下寒,燮理阴阳,具有安蛔制蛔、调肝理脾等功效,临床应用广泛.凌江红教授认为,乌梅丸与难治性功能性胃肠病病机相参、方证相应,在临证中常用乌梅丸加减治疗功能性胃肠病,效果颇佳.兹分享其临证思路和验案如下,以期为中医药治疗难治性功能性胃肠病提供临床新思路.

Ethnopharmacological relevance: Chaihu Shugan Powder (CHSGP) has significant clinical efficacy in the treatment of functional dyspepsia (FD), but the specific mechanism requires further study. Aim of study: The aim of this study was to investigate the therapeutic effect of CHSGP on FD rats and the underlying mechanism of the effect on interstitial cells of cajal (ICC) mitophagy. Materials and methods: The tail-clamping stimulation method was utilized to establish an FD rat model in vivo. Gastric emptying rate and small intestinal propulsion rate test, H&E staining, and Immunohistochemistry were conducted to evaluate the therapeutic effects of CHSGP on FD rats. In vitro, the regulatory effect of CHSGP on CCCP-mediated ICC mitophagy was further investigated by CCK8, Transmission electron microscope, immunofluorescence co-staining, Quantitative polymerase chain reaction and Western blot to reveal the potential mechanisms of CHSGP inhibited ICC mitophagy. Results: Animal experiments provided evidence that CHSGP promoted gastric motility, increased ICC numbers, reduced Parkin expression, and elevated USP30 expression in FD rats. In vitro, further mechanism research demonstrated that CHSGP decreased LC3II/LC3I,PINK1,Parkin,PHB2 protein expression and increased USP30 protein expression. Furthermore, CHSGP increased Mfn2 protein expression by suppressing activation of the PINK1/Parkin pathway when USP30 is knocked down, consequently reducing CCCP-induced ICC mitophagy. Conclusions: These results suggest that CHSGP may treat FD against CCCP-induced ICC mitophagy by the upregulation of via PINK1/Parkin pathway.

BACKGROUND: Chaihu Shugan powder (CSP) is a prevalent prescription product used in the treatment functional dyspepsia (FD) in China. However, the underlying pharmacological mechanisms involved in the treatment of FD remain unclear. OBJECTIVE: To explore the key components of CSP and their molecular targets and mechanisms in the treatment of FD. METHODS: Active compounds for CSP were identified from the TCMSP and SymMap databases, and the relevant targets were predicted. FD-related targets were obtained from the GeneCards and CTD database. In addition, using the protein-protein interactions (PPI) analysis, the common targets were obtained. Furthermore, the compound-target networks were created with Cytoscape. Finally, molecular docking was performed to identify the core targets and validate them experimentally. RESULTS: In total, 78 active compounds and 671 related targets of CSP were obtained. PPI network analysis identified 15 key FD-related compound targets. Molecular docking revealed that sitosterol and hyndarin exhibited good binding activities with AKT1 and IL6, respectively. Animal experiments have shown that CSP effectively increased the protein levels of AKT1 and reduced the serum levels of IL-6 in FD rats. CONCLUSION: This study provides a theoretical evidence for the analysis of the molecular targets and mechanisms of the action of CSP in FD.

Context Chaihu Shugan San (CHSGS) was effective in the treatment of functional dyspepsia (FD).Objective To investigate the mechanism of CHSGS in FD through dynamin-related protein 1 (Drp-1)-mediated interstitial cells of cajal (ICC) mitophagy.Materials and methods Forty Sprague-Dawley (SD) rats were randomly divided into control, model, mdivi-1, mdivi-1 + CHSGS and CHSGS groups. Tail-clamping stimulation was used to establish the FD model. Mdivi-1 + CHSGS and CHSGS groups were given CHSGS aqueous solution (4.8 g/kg) by gavage twice a day. Mdivi-1 (25 mg/kg) was injected intraperitoneally once every other week for 4 w. Mitochondrial damage was observed by corresponding kits and related protein expressions were assessed by Immunofluorescence and (or) Western Blot.Results Compared with the mean value of the control group, superoxide dismutase (SOD) and citrate synthase (CS) in the model group were decreased by 11% and 35%; malondialdehyde (MDA) and reactive oxygen species (ROS) were increased by 1.2- and 2.8-times; ckit fluorescence and protein expressions were decreased by 85% and 51%, co-localization expression of LC3 and voltage dependent anion channel 1 (VDAC1), Drp-1 and translocase of the outer mitochondrial membrane 20 (Tom20) were increased by 10.1- and 5.4-times; protein expressions of Drp-1, Beclin-1, and LC3 were increased by 0.5-, 1.4-, and 2.5-times whereas p62 was decreased by 43%. After mdivi-1 and (or) CHSGS intervention, the above situation has been improved.Discussion and conclusion CHSGS could improve mitochondrial damage and promote gastric motility in FD rats by regulating Drp-1-mediated ICC mitophagy.

Precancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats. The chemical ingredients of ELG were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Specific Pathogen Free SD rats were randomly assigned to 3 groups: the control, model, and ELG groups. The 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) integrated modeling method was adopted to construct the PLGC rat model in groups except for the control group. Meanwhile, normal saline was used as an intervention for the control and model groups, and ELG aqueous solution for the ELG group, lasting 40 weeks. Subsequently, the stomach of rats was harvested for further analysis. Hematoxylin-eosin staining of the gastric tissue was conducted to assess the pathological changes. Immunofluorescence was carried out for the expression of CD68, and CD206 proteins. Real-time quantitative PCR combined with Western blot was conducted to analyze the expression of arginase-1(Arg-1), inducible nitric oxide synthase (iNOS), p65, p-p65, nuclear factor inhibitor protein-α (IκBα), and p-IκBα in gastric antrum tissue. Five chemical ingredients including Curcumol, Curzerenone, Berberine, Ferulic Acid, and 2-Hydroxy-3-Methylanthraquine were identified in ELG. The gastric mucosal glands of rats treated with ELG were orderly arranged, with no intestinal metaplasia and no dysplasia. Furthermore, ELG decreased the percentage of M2-type TAMs marked with CD68 and CD206 proteins, and the ratio of Arg-1 to iNOS in the gastric antrum tissue of rats with PLGC. In addition, ELG could also down-regulate the protein and mRNA expression of p-p65, p65, and p-IκBα, but up-regulate the expression of IκBα mRNA in rats with PLGC. The results showed that ELG attenuates PLGC in rats by suppressing the M2-type polarization of tumor-associated macrophages (TAMs) through NF-κB signaling pathway.

Ethnopharmacological relevanceUlcerative colitis is classified as one of the modern intractable diseases by the World Health Organization, and the application of traditional Chinese medicine to ulcerative colitis is also evident. Frankincense has been used for centuries as a traditional medicine for the treatment of various diseases, especially inflammatory diseases, chronic bowel diseases and some other diseases. It has been used in the treatment of Crohn's disease and ulcerative colitis in many countries, including Africa, China, India, and the Middle East.Aim of the studyFrankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives. Materials and methodsThe FREO components were analyzed by GC-MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, "quantity-effect" weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay and immunohistochemistry. The expression of MAPK and NF-κB-related proteins by the Western Blotting method.ResultsFREO mediates its therapeutic effects on UC via the synergistic action of its active components. Treatment with FREO significantly alleviated the symptoms and increased the loss of cupric cell in UC mice, and the expression of inflammatory cytokines such as TNF-α and IL-6 was decreased. In addition, FREO inhibited the phosphorylation of ERK and p65 in MAPK and NF-κB. ConclusionsFREO acts on the CACNA1C target via Hepten-2-yl tiglate, 6-methyl-5-, downregulates Ras to impair ERK activation and further inhibits NF-κB/P65 activation and its nuclear translocation to suppress the inflammatory response through the MAPK/NF-κB pathway thereby improving UC symptoms. This study provides a promising drug candidate and a new concept for the treatment of UC.

Abstract Context Elian Granules have been applied in the treatment of precancerous lesions of gastric cancer (PLGC) and achieved good results. However, its exact mechanism remains unclear. Objectives To explore the mechanism of Elian granules in treating PLGC through the mitogen-activated protein kinase (MAPK) signalling pathway based on network pharmacology. Materials and methods Through network pharmacological methods, the targets of the active component of Elian granules against PLGC were obtained. Subsequently, Specific Pathogen Free (SPF) male Sprague Dawley (SD) rats were randomly divided into normal, model, and Elian granule groups. The N-methyl-N′-nitro-N-nitrosoguanidine comprehensive method was used to establish the PLGC rat model. The model and Elian granule groups were given normal saline and Elian granule aqueous solution (3.24 g/kg/d) intragastric administration, respectively, for 24 weeks. The pathological changes in gastric tissues were observed by hematoxylin-eosin staining. The protein expression of p-JNK and p-p38 was verified by western blotting. Results 394 and 4,395 targets were identified in Elian granules and PLGC, respectively. The 190 common targets were mainly enriched in MAPK signalling pathways. The gastric mucosal epithelium was still intact, the glands were arranged regularly, and no goblet cells or apparent inflammatory cell infiltration were observed in the Elian granule group. The expression of p-JNK and p-p38 protein of the Elian granule group (0.83 ± 0.08; 1.18 ± 0.40) was significantly higher than the model group (0.27 ± 0.14; 0.63 ± 0.14) (p < 0.01; p < 0.05). Discussion and conclusions Elian granules may play a critical role in the treatment of rat PLGC by up-regulating the expression of p-JNK and p-p38 proteins in the MAPK signalling pathway, thus providing a scientific basis for clinical application.

线粒体自噬是指为了维持细胞内环境稳定而通过选择性自噬来降解功能失调或过剩的线粒体.在众多线粒体自噬相关通路研究中,对Pink1/Parkin信号通路的探索较为详细.在哺乳动物细胞中,Ser/Thr蛋白激酶Pink1和E3泛素连接酶Parkin协同作用,感知线粒体功能状态并对受损的线粒体进行标记,以促进其通过自噬途径进行降解.同时,泛素化和去泛素化在调节Parkin和线粒体自噬活性中起着重要的作用.本文就Pink1/Parkin信号通路以及去泛素化酶在线粒体自噬中的作用进行综述.

目的 基于网络药理学探讨莪术—黄连药对治疗慢性萎缩性胃炎(CAG)的作用机制.方法 利用TC-MSP数据库分别检索莪术、黄连化学成分及靶点基因,并通过Cytoscape软件构建药对—成分—靶点基因网络;利用GeneCards数据库获得CAG疾病靶点;将莪术—黄连药对有效成分靶点基因和CAG相关靶点基因同时录入VENNY2.1软件,构建维恩图以获取交集基因,获得药对与CAG疾病的共同靶点.挑选共同靶点基因中度值前25位的基因,通过String数据库构建蛋白—蛋白相互作用(PPI)网络,对网络特征进行分析,根据度值预测各节点的重要性;通过DAVID数据库对交集基因进行GO富集分析和KEGG通路分析.最后通过Cytoscape软件构建药对—成分—靶点基因—信号通路与疾病靶点相互作用网络,根据度值预测治疗节点.结果 莪术—黄连药对共筛选出12个化学成分药动学特征良好的活性成分,得到靶点基因180个;CAG靶点基因639个;二者交集基因78个,度值排名前3位的基因为AKT1、IL-6、PTGS2;78个基因的生物学功能涉及凋亡过程的负调控、酶结合、相同蛋白结合等,以及TNF信号通路、MAPK信号通路、Toll样受体信号通路、HIF-1信号通路、NF-κB信号通路、p53信号通路.结论 莪术—黄连药对可能是通过调节AKT1、IL-6等靶点基因和TNF信号通路、MAPK信号通路,从而发挥抗CAG作用.

Hesperidin is one of the main active ingredients of Citrus aurantium L. (Rutaceae) and tangerine peel, which have anti-inflammatory and antioxidant effects. In previous study, we found that gastric motility disorder in functional dyspepsia (FD) rats accompanied by excessive autophagy/mitochondrial swelling and even vacuolization in the interstitial cells of cajal (ICC), but the exact mechanism has not yet been investigated. Therefore, we used different doses of hesperidin (50 mg/kg, 100 mg/kg, and 200 mg/kg) to intervene in FD rats, and found that medium doses of hesperidin (100 mg/kg) significantly increased gastric motility in FD rats. Subsequently, FD rats were randomly divided into control group, model group, mdivi-1 group, mdivi-1+hesperidin group and hesperidin group, and mitochondrial division inhibitor (mdivi-1) was injected intraperitoneally to further investigate whether hesperidin could regulate dynamin-related protein 1 (Drp1)-mediated mitophagy in ICC to improve mitochondrial damage. The results showed that compared with the model group, the serum malondialdehyde (MDA) level decreased and the superoxide dismutase (SOD) level increased in the mdivi-1 and hesperidin groups (p < 0.001). Transmission electron microscopy (TEM) observed that the mitochondrial nuclear membrane was intact in gastric tissues with a clear internal cristae pattern, and autophagy lysosomes were rare. The co-localization expression of microtubule associated protein 1 light chain 3 (LC3) and voltage dependent anion channel 1 (VDAC1), Drp1 and translocase of the outer mitochondrial membrane 20 (Tom20) was significantly decreased (p < 0.001), the protein expression of mitochondrial Drp1, Beclin1 and LC3 were significantly decreased (p < 0.001), the protein expression of mitochondrial P62 and ckit in gastric tissue were significantly increased (p < 0.05, p < 0.001). The above situation was improved more significantly by the synergistic intervention of mdivi-1 and hesperidin. Therefore, hesperidin can improve mitochondrial damage and promote gastric motility in FD rats by regulating Drp1-mediated ICC mitophagy.

目的 基于网络药理学方法探讨枳实治疗功能性消化不良(FD)的潜在作用机制.方法 通过中药系统药理学数据库与分析平台(TCMSP)筛选枳实的主要活性成分,并通过中国知网数据库(CNKI)检索文献报道的枳实活性成分进行补充.利用TCMSP数据库检索枳实活性成分的作用靶点.通过Genecards数据库获取FD相关疾病靶点.将活性成分靶点与FD疾病靶点相映射后取交集,得到枳实治疗FD的共同靶点(关键靶点).将共同靶点导入STRING数据库构建靶点蛋白互作(PPI)网络,再利用Cytoscape3.6.0软件进行可视化处理,筛选核心靶点.应用DAVID 6.8数据库对共同靶点进行GO功能和KEGG通路富集分析.结果 共获得枳实活性成分19个,包括木犀草素、柚皮素、川陈皮素等核心成分,作用于AKT1、TNF、IL6、VEGFA、PTGS2、CASP3等54个关键靶点;参与RNA聚合酶Ⅱ启动子转录、凋亡、药物的反应等生物过程;主要调控PI3K-Akt、TNF、T细胞受体、雌激素、甲状腺激素、神经营养因子等35条信号通路.结论 枳实可能通过多成分、多靶点、多通路,从调控细胞凋亡、抑制炎症反应等多方面发挥对FD的治疗作用.

胃肠动力障碍性疾病是一类以胃肠动力异常为主要发病机制的临床常见病,包括肠易激综合征、功能性消化不良、糖尿病胃轻瘫等.近十余年来随着微生物测序技术的迅猛发展,人们对肠道菌群的了解日益深入,普遍发现胃肠动力障碍性疾病存在肠道菌群的紊乱.关于肠道菌群与胃肠动力的相关性研究也取得了一些进展,本文就肠道菌群与胃肠动力的关系及二者相互作用的机制作一综述.

[目的]探讨N-甲基-N'-硝基-N-亚硝基胍(MNNG)综合法诱导大鼠胃癌(GC)形成过程中胃组织病理学形态与超微结构的变化.[方法]将36只SPF级雄性SD大鼠随机分为正常组与模型组各18只,正常组予常规自由饮食,模型组自由饮用170μg/ml MNNG溶液,喂食含0.03％雷尼替丁饲料,灌服2％水杨酸钠溶液配合饥饱失常法复制GC大鼠模型,于造模后20、24、28、32、48周观察两组大鼠的胃黏膜病理学形态与超微结构的变化.[结果]随着造模时间的增加,模型组大鼠在造模第24周出现肠上皮化生,32周出现异型增生,48周癌变.[结论]MNNG综合法诱导下大鼠胃黏膜肠上皮化生和异型增生向癌症转变可能发生在造模第32～48周,与胃黏膜上皮细胞结构异常有关.

目的:观察柴胡疏肝散对功能性消化不良(FD)模型大鼠胃动力、胃组织线粒体功能及线粒体自噬的影响,揭示柴胡疏肝散防治FD的作用机制.方法:将32只SPF级SD大鼠适应性喂养1周后随机分为正常组、模型组、柴胡疏肝散组(4.8 g·kg-1),多潘立酮组(4.5 mg·kg-1),每组8只.除正常组外,其余3组均采用改良夹尾刺激法复制FD大鼠模型.4周后,采用营养性半固体糊法观察FD大鼠胃排空率,酶联免疫吸附测定法(ELISA)检测血清柠檬酸合成酶(CS),胃动素(MTL),胃泌素(GAS)含量,苏木素-伊红(HE)染色观察胃组织病理变化,透射电镜观察线粒体特征,免疫荧光共定位法观察胃组织微管相关蛋白1轻链3(LC3)与电压依赖性阴离子通道蛋白1(VDAC1)表达,提取新鲜胃组织线粒体,生化试剂盒检测线粒体活性氧(ROS),丙二醛(MDA)水平,超氧化物歧化酶(SOD)含量,蛋白免疫印迹法(Western blot)检测线粒体LC3,自噬关键分子酵母Atg6同系物(Beclin1),p62蛋白表达.结果:与正常组比较,模型组大鼠胃排空率显著降低(P＜0.01),血清CS,MTL,GAS含量显著降低(P＜0.01),HE染色可见各组大鼠胃组织未见糜烂、溃疡等病理改变,透射电镜观察胃组织线粒体肿胀、扩张,出现空泡病变,LC3和VDAC1免疫荧光共定位表达显著增加(P＜0.01),线粒体ROS,MDA含量显著升高(P＜0.01),SOD含量显著降低(P＜0.01),LC3,Beclin1蛋白表达水平明显升高(P＜0.05,P＜0.01),p62蛋白表达水平明显下降(P＜0.05);与模型组比较,柴胡疏肝散组和多潘立酮组大鼠胃排空率均明显升高(P＜0.05),血清CS,MTL,GAS含量明显升高(P＜0.05,P＜0.01),透射电镜观察胃组织线粒体核膜完整,内部嵴形态清晰,嵴密度较高,部分存在线粒体分裂融合现象,LC3和VDAC1共定位表达显著减少(P＜0.01),线粒体ROS,MDA含量均明显降低(P＜0.05,P＜0.01),SOD含量明显升高(P＜0.05),LC3,Beclin1蛋白表达水平明显降低(P＜0.05,P＜0.01),p62蛋白表达水平显著升高(P＜0.01).结论:柴胡疏肝散防治FD的作用机制可能与改善胃组织线粒体功能、抑制线粒体自噬有关.

目的:探讨莪连颗粒对胃癌大鼠胃组织自噬及磷酯酰肌醇-3激酶（PI3K）/蛋白激酶B（PKB/Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的影响。方法:SPF级SD大鼠随机分为正常组、模型组、莪连颗粒组和胃复春组。除正常组常规饲养外,模型组、莪连颗粒组及胃复春组使用N-甲基-N’-硝基-N-亚硝基胍（MNNG）综合法诱导构建胃癌大鼠模型,并分别予以生理盐水、莪连颗粒水溶液（3.240 g·kg（-1））及胃复春水溶液（0.390 g·kg（-1））灌胃,连续48周。剖腹取胃,肉眼观察胃大体改变,采用苏木素-伊红（HE）染色观察大鼠胃组织病理学变化,实时荧光定量聚合酶链式反应（Real-time PCR）及蛋白免疫印迹法（Western blot）检测大鼠胃组织微管相关蛋白1轻链3β（LC3B）,Beclin1,p62,PI3K,Akt,mTOR mRNA及蛋白表达。结果:与正常组比较,模型组大鼠胃胀大,胃壁变薄,胃黏膜色泽苍白,皱襞萎缩浅平,走行紊乱,可见结节及赘生物;与模型组比较,莪连颗粒组大鼠胃胀大减轻,胃壁变薄改善,胃黏膜色暗,皱襞减少,走行尚规整,偶见细颗粒状结节。HE染色显示,与正常组比较,模型组大鼠胃组织腺体排列拥挤紊乱,形态多样,细胞形态不一,胞浆嗜碱性,核大深染不规则,可见核分裂像,黏膜肌层浸润破坏;与模型组比较,莪连颗粒组大鼠胃组织腺体排列尚规整,少部分可见轻度异型细胞。与正常组比较,模型组大鼠胃组织LC3B,Beclin1 mRNA和蛋白表达明显降低（P＜0.05）,PI3K,p62,Akt及mTOR mRNA和蛋白表达明显升高（P＜0.05）;与模型组比较,莪连颗粒组胃组织LC3B,Beclin1 mRNA和蛋白表达明显升高（P＜0.05）,PI3K mRNA及p62,Akt,mTOR mRNA和蛋白表达明显降低（P＜0.05）。结论:莪连颗粒可改善胃癌大鼠胃组织细胞异型性,其机制可能与抑制PI3K/Akt/mTOR信号通路促进自噬相关。