Background: The intestinal barrier is crucial for maintaining gastrointestinal homeostasis by preventing pathogen invasion and systemic disorders. A high-fat diet (HFD) leads to lipid dysregulation, chronic inflammation, and endoplasmic reticulum stress (ERS), which collectively disrupt intestinal barrier integrity. Saponins from Panax japonicus (SPJ), known for their antiinflammatory and metabolic regulatory properties, were investigated for their potential protective effects. Methods: This study investigated the protective effects of SPJ against HFD-induced intestinal barrier dysfunction and the role of the Mfn2-PERK signaling axis. In vivo, HFD-fed mice were treated with SPJ and assessed for jejunal barrier integrity (claudin-1, ZO-1), inflammatory responses, ERS markers, mitochondrial morphology, and Mfn2 expression. In vitro, Caco-2 cell monolayers were pretreated with the PERK agonist CCT020312 and/or SPJ for 1 h, followed by palmitic acid (PA) exposure for 24 h to induce lipotoxicity. Protein expression of claudin-1 and Mfn2 was analyzed by Western blot to evaluate epithelial permeability and mitochondrial-ER regulatory mechanisms. Results: SPJ treatment restored intestinal barrier function in HFD-fed mice, as evidenced by elevated expression of claudin-1 and ZO-1, and significantly alleviated HFD-induced jejunal inflammation and ERS. HFD induced mitochondrial fragmentation accompanied by reduced Mfn2 expression, which were effectively reversed by SPJ treatment. Consistent with in vivo findings, SPJ reduced PA-induced hyperpermeability, upregulated Mfn2, and inhibited PERK pathway activation in Caco-2 monolayers. Further mechanistic validation revealed that co-treatment with the PERK agonist CCT020312 attenuated SPJ-mediated claudin-1 upregulation, confirming PERK pathway dependency for barrier protection. Notably, SPJ maintained Mfn2 upregulation even under PERK activation. Conclusions: We conclude that SPJ ameliorate HFD-and PA-induced intestinal barrier dysfunction by upregulating Mfn2 to enhance mitochondria-ER interactions and attenuating PERK-mediated ERS. These findings highlight SPJ as a potential therapeutic agent for metabolic stress-associated intestinal disorders.

BACKGROUND/OBJECTIVES:Chronic high-fat diet (HFD) consumption induces low-grade intestinal inflammation. Although saponins from Panax japonicus (SPJs) have anti-inflammatory properties, the mechanisms by which they mitigate HFD-induced jejunal inflammation remain unclear. This study examined whether SPJs alleviate inflammation by modulating lipid metabolism and endoplasmic reticulum stress (ERS) in the jejunum. MATERIALS/METHODS:HFD-fed mice were administered high-dose SPJs extract. The jejunal triglyceride (TG) levels, gene expression related to TG synthesis (glycerol-3-phosphate acyltransferase 3 [Gpat3] and diacylglycerol O-acyltransferase 2 [Dgat2]) and lipolysis (adipose triglyceride lipase [Atgl]), cytosolic lipid droplets (CLDs) deposition, ERS markers, and inflammatory responses were assessed. RESULTS:HFD feeding induced TG accumulation, upregulated Gpat3 and Dgat2, downregulated Atgl, and promoted CLDs deposition in jejunal epithelial cells. High-dose SPJs attenuated these changes. Furthermore, SPJs suppressed HFD-induced ERS and inflammation in the jejunum. In particular, short-term HFD exposure initially enhanced the antioxidant responses without significant ERS activation. CONCLUSION:SPJs ameliorate HFD-induced jejunal inflammation by modulating lipid metabolic genes, reducing intracellular lipid accumulation, and alleviating ERS. These findings highlight the role of lipid-driven ERS in gut inflammation and the potential of SPJs as a therapeutic intervention.

Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice. Moreover, CS treatment also inhibited the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs). Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed HFD-induced NF-κB signaling in vivo and LPS-induced NF-κB activation as reflected by the fact that their phosphorylated forms and the ratios of pNF-κB/NF-κB, pIKK/IKK, and pIκB/IκB were all decreased in EAT from HFD-fed mice treated with CS as compared with those of HFD mice. Taking together, this study has revealed that CS effectively inhibits HFD-induced inflammation in adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and NF-κB signaling. Thus, CS can serve as a potential therapeutic drug in the prevention and treatment of inflammation-associated diseases.

BackgroundLipopolysaccharide (LPS) is an endotoxin that causes inflammation, and the content of LPS increases gradually during the process of aging. Whether the response of the colon to LPS stimulation will increase with age is yet unknown.ObjectiveThe study investigated the effects of LPS stimulation on the colon of adult and aging rats.Method43 healthy male SD rats were divided into 4 different groups: adult group and LPS-stimulated adult group at the age of 4 months, and aging group and LPS-stimulated aging group at the age of 22 months. Rats were stimulated by intraperitoneal injection of LPS (1mg/kg) for 24 h. The morphological changes of the colon were observed, and intestinal inflammatory response, tight junction proteins, apoptosis, and proliferation in intestinal epithelial cells were detected.ResultsA series of morphology changes occurred in the colon of adult rats after LPS stimulation, the higher inflammatory response (TLR4, NF-κB, and IL-1β), changes in the protein levels of tight junctions (ZO-1, Claudin1, and Claudin2), and increased apoptosis (Bax, Bcl2) and proliferation (PCNA) of intestinal epithelial cells. The above changes were also found in aging rats. LPS stimulation further promotes the above changes to some extent in the colon of aging rats.ConclusionA series of colon changes in rats was significantly damaged during LPS stimulation and aging, and these changes were further aggravated to some extent in LPS-stimulated aging rats.

病理学是基础医学和临床医学之间的重要桥梁课程,是医学本科教育中的核心专业课程.开展顺应新时代发展要求的病理学课程教学改革实践对培养高素质、强能力的医学专门人才具有重要意义,对我国医学科学发展和疾病防治具有重要意义.文章旨在探索课程思政有机融入病理学教学过程中的途径及思路.

新形势下,课程思政是高校教育改革的重要内容;人体解剖学蕴含丰富的思政内容,具有得天独厚的课程思政的优势,同时其授课对象更有课程思政的需求和必要性.人体解剖学教师应充分挖掘思政元素,把人文精神、职业操守、社会与民族情怀、马列主义原理等思政内容有机融入课程中,达到教书育人的终极目标.

Impaired tight junction (TJ) function and autophagy and the activated p38 mitogen-activated protein kinase (MAPK)/matrix metalloproteinase 9 (MMP9) pathway in Sertoli cells cause spermatogenic disorders. However, it is unclear whether reduced TJ barrier function and autophagy and the activated p38 MAPK/MMP9 pathway in Sertoli cells are closely associated with age-related testicular dysfunction. Thus, we evaluated these changes in Sertoli cells using 6-, 12-, 18-, and 24-month-old Sprague-Dawley rats. The results showed that testicular morphology gradually degenerated, as evidenced by increased exfoliated germ cells, decreased seminiferous tubule diameter and seminiferous epithelium height, and reduced the numbers of spermatogonia, primary spermatocytes and spermatids during the process of aging. In addition, the TJs formed by adjacent Sertoli cells were progressively destroyed accompanied by an abnormal ultrastructure and decreased expression of the TJ proteins zonula occludens-1 (ZO-1), occludin, and claudin-11 with aging. Furthermore, the expression of phosphorylated p38MAPK and MMP-9 in Sertoli cells and testis gradually increased, and the expression of occludin co-localizated with MMP-9 progressively decreased. Meanwhile, autophagy levels also gradually decreased, including decreased autophagic vacuole formation and weak expression of light chain 3 (LC3) and autophagy-related 5 (Atg5) in Sertoli cells. Taken together, our results indicate that aging causes impaired TJ barrier function and degeneration of seminiferous tubules. The mechanism might be related to the activated p38MAPK/MMP9 pathway and inactivated autophagy in Sertoli cells.

Perfluorooctane sulfonate (PFOS) is widely recognized as causing Sertoli cell injury and testicular toxicity in males. Icariin is a flavonoid from Epimedium, which effectively improves spermatogenesis disturbance induced by several factors in clinic. However, it is unclear whether icariin improves PFOS-induced testicular toxicity. In vivo, fifty-two male mice were randomly separated into four groups: normal control group, model group, and low and high doses of icariin-treated groups, with 13 mice in each group. Except for the normal control group, the mice in the model group and icariin-treated groups were administered PFOS (10 mg kg-1) by gavage daily for 28 consecutive days, and concurrently treated with a diet containing different doses of icariin (0, 5 or 20 mg kg-1). In vitro, TM4 cells were treated with 150 μM PFOS to induce Sertoli cell injury, and were then utilized for icariin treatment. Our results demonstrated that icariin attenuated PFOS-induced testicular toxicity by increasing the testicular, epididymal and seminal vesicle weights, epididymal and seminal vesicle indices, sperm parameters, and seminiferous epithelium height. In addition, icariin improved the PFOS-induced blood-testis barrier (BTB) disruption by alleviating the Sertoli cell junctional injury, but without affecting Sertoli cell numbers in the testis of mice. Moreover, icariin increased the expression levels of tight junction proteins (ZO-1, Occludin and Claudin-11) and gap junction proteins (CX43 and p-CX43), and decreased the expression levels of p-p38MAPK and matrix metalloproteinase 9 (MMP9) both in vivo and in vitro. Furthermore, alleviation of the Sertoli cell injury by icariin exerted similar effects as SB203580 (an inhibitor of p38MAPK) in TM4 cells. This study revealed that icariin effectively reduces PFOS-induced testicular toxicity by alleviating the Sertoli cell injury and downregulating the p38MAPK/MMP9 pathway, indicating that icariin may be an attractive dietary supplement for the intervention of PFOS-induced testicular dysfunction.

Inflammatory cytokines including TNF-α and IL-1β impair intestinal barrier function in aging by disrupting intestinal tight junction integrity. Icariin (ICA) has a variety of pharmacological effects. Indeed, ICA produces anti-inflammatory, anti-oxidative stress, and inhibitory effects on microRNA (miRNA) expression. This study was to explore whether ICA could alleviate inflammation-associated intestinal barrier function impairment in aging and its underlying mechanism. Of particular interest, network pharmacology prediction indicated the potential therapeutic impacts of ICA for the treatment of colitis. Then, rats were used to study whether ICA has a protective effect on the reduction of tight junctions caused by inflammatory cytokines. Next, Caco-2 cell monolayers were used to explore the mechanism by which ICA alleviates the down-regulation of tight junctions. Network pharmacology prediction revealed that ICA alleviated colitis via suppressing oxidative stress. After ICA intervention, expressions of inflammatory cytokines were reduced, but tight junctions, antioxidant enzymes in aging rats were up-regulated. ICA reversed the TNF-α-induced decrease in abundance of Occludin protein in Caco-2 cell monolayers. Meanwhile, ICA alleviated the increase in permeability and expression of miR-122a. However, the protective effect of ICA was markedly attenuated after transfection with miR-122a mimics. In conclusion, ICA reduced the expressions of Occludin, Claudin1, and Claudin5 in colon, which were related to the reduction of TNF-α and IL-1β and alleviation of colonic in vivore. And ICA attenuated TNF-α-induced Occludin disruption and epithelial barrier impairment by decreasing miR-122a expression in Caco-2 cell monolayers.

基于案例的学习(CBL)的特点是使用真实的临床案例、活跃的小组学习、激活现有知识和应用新获得的知识.利用基于案例的学习(CBL)对提高学生对基础知识的认识和理解及发展学生的临床推理技能方面是不可或缺的.

案例学习被认为是提高学生知识转移能力的一种有效的教学方法,基础科学具有特殊的重要性,因为它们是医学生进入临床前几年学习的第一门课程.本科医学课程的临床前阶段必须嵌入临床相关的学习经验,以连接基础科学和临床学科.随着在医学课程中引入综合教学方法,有必要以一种与真实临床场景相关的方式教授基础科学.以学生为中心的教育方法,基于案例的学习(CBL)教育方法是通过多种方法锚定一个临床病例进行.CBL通过更结构化的方法,由教师专家引导调查,促进讨论与预先确定的问题,并以重点学习点结束.本文探讨了案例学习及其在医学基础教育中如生物化学,生理学等基础课程的应用研究及意义.

Introduction: Microglia-mediated inflammatory responses play a crucial role in aging-related neurodegenerative diseases. The TXNIP/NLRP3 pathway is a key pathway leading to microglial activation. Panax notoginseng Saponins (PNS) have been widely used for the treatment of stroke in China. Objective: This study evaluates the anti-neuroinflammatory effect of PNS and investigates the mechanism via TXNIP-mediated NLRP3 inflammasome activation in aging rats. Materials and Methods: Eighteen-month-old Sprague-Dawley rats were randomly divided into the aging control group and PNS treated groups (n=15 each group). For PNS-treated groups, rats were administrated food with PNS at the doses of 10 mg/kg and 30 mg/kg for consecutive 6 months until they were 24-month old. Rats from the aging control group were given the same food without PNS. Twomonth- old rats were purchased and given the same food until they were 6-months old as the adult control group (n = 15). Then, the cortex and hippocampus were rapidly harvested and deposited. H&E staining was used to assess histo-morphological changes. Western blotting was carried out to detect the protein expression. Immunofluorescence was employed to measure the co-localization of NLRP3, TXNIP and Iba-1. In vitro model was established by LPS+ATP co-incubation in the BV2 microglia cell line. Results:: Aging rats exhibited increased activation of microglia, accompanied by a high level of IL-1β expression. Meanwhile, aging rats showed enhanced protein expression of TXNIP and NLRP3 related molecules, which co-localized with microglia. PNS treatment effectively reduced the number of degenerated neurons and reversed the activation of the TXNIP/NLRP3 inflammatory pathway. In vitro results showed that PNS up to 100 μg/ml had no significant toxicity on BV2 microglia. PNS (25, 50 μg/ml) effectively reduced the inflammatory response induced by LPS and ATP co-stimulation, thus inhibiting the expression of TXNIP/NLRP3 pathway-related proteins. Discussion and Conclusion: PNS treatment improved aging-related neuronal damage through inhibiting TXNIP mediated NLRP3 inflammasome activation, which provided a potential target for the treatment of inflammation-related neurodegenerative diseases.

潘氏细胞是重要的微环境信号分子提供者,可为小肠干细胞(intestinal stem cells,ISCs)提供Wnt、Notch、EGF、mTORC1等相关信号因子,维持干细胞的增殖和分化平衡.对潘氏细胞提供ISCs微环境信号因子,以及潘氏细胞相关信号因子变化导致的小肠上皮稳态失调进行概述,旨在为潘氏细胞和ISCs相互作用的研究提供思考,为相关小肠上皮稳态失调提供新的治疗思路.

目的 探讨竹节参总皂苷对高脂饮食小鼠小肠上皮分泌型细胞数量的调节作用.方法 将40只Balb/c小鼠随机均分为4组,即对照组,高脂模型组和竹节参总皂苷高、低剂量组.对照组小鼠给予普通维持饲料,高脂模型组和竹节参总皂苷高、低剂量组小鼠均给予高脂饲料;另外,竹节参总皂苷高、低剂量组小鼠每天给予45,15 mg·kg-1的竹节参总皂苷分别进行灌胃处理,高脂模型组和对照组以生理盐水进行灌胃,灌胃频次均为每天1次,每周6d.各组小鼠均持续喂养7个月后处死,取材并进行HE染色观察各组高脂饮食小鼠回肠组织病理学改变,阿利新蓝染色、过碘酸-Schiff染色后统计小鼠回肠杯状细胞数量,荧光桃红酒石黄染色后统计小鼠潘氏细胞数量,免疫组化法检测小鼠回肠Lysozyme、HES1蛋白的表达.结果 与高脂模型组相比,竹节参总皂苷高剂量组小鼠回肠绒毛长度与隐窝深度比值、黏膜下层厚度显著降低(P＜0.05),内环肌层厚度显著增加(P＜0.01),Lysozyme蛋白表达、杯状细胞数量显著增加(P＜0.05或P＜0.001),HES1蛋白表达显著下调(P＜0.01).结论 竹节参总皂苷通过抑制高脂饮食小鼠小肠HES1蛋白的表达调节小肠上皮分泌型细胞数量.

Accumulation of oxidative stress, DNA damage and impaired DNA repair appear to play critical roles in the decline of testicular function with aging. However, when those factors begin to lose control in testis during aging has not yet been well understood. This study was designed to assess the changes of oxidative stress and DNA damage status, and DNA repair capacity in testis during aging. Thus, male Sprague-Dawley rats at 3, 9, 15 and 24 months of age were used to delineate the dynamic changes in testicular weight and index, testosterone concentration, testicular histology, Nrf2-mediated oxidative stress, DNA damage, DNA repair and apoptosis. Results showed that testicular weight and index, testosterone concentration and spermatid number progressively declined from 9 to 24 months of age. Similarly, seminiferous tubule diameters and seminiferous epithelium heights gradually diminished with aging. Nrf2-mediated antioxidant defense ability was significantly impaired in testis with increasing age including decreased the activity of SOD and the expression levels of Nrf2, HO-1 and NQO-1, and increased the contents of MDA. In addition, DNA damage including DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) also progressively increased accompanied by increased levels of 8-hydroxydeoxyguanosine (8-OHdG) and γ-H2AX, and activated ATM/Chk2 and ATR/Chk1 pathway. Consistent with the results of Nrf2 pathway, the expression levels of APE1, OGG1 and XRCC1 involved in base excision DNA repair (BER) pathway increased from 3 to 9 months of age, and then gradually decreased after 9 months of age. Finally, TUNEL and Western blot results further confirmed germ cell apoptosis progressively increased from 3 to 24 months of age as evidenced by decreased ratio of Bcl-2/Bax and levels of Bcl-2 expression, and increased Bax expression levels. Taken together, our results suggest that downregulation of antioxidant ability mediated by Nrf2 pathway and impairment of BER capacity might correlate with increased DNA damage, and then induce declining testicular function during aging after adult.

BACKGROUND:Oxidative stress and mitochondrial dysfunction play a vital role in the pathogenesis of brain aging. Saponins from Panax japonicus (SPJ) have attracted much attention for their potential to attenuate age-related oxidative stress as the main ingredient in rhizomes of Panax japonicus.OBJECTIVE:This study aimed to investigate the neuroprotective effects of SPJ on natural aging rats as well as the underlying mechanisms regarding oxidative stress and mitochondrial pathway.METHODS:Sprague-Dawley rats were divided into control groups (3-, 9-, 15- and 24-month old groups) and SPJ-treated groups. For SPJ-treated groups, SPJ were orally administrated to 18-month old rats at doses of 10 mg/kg, 30 mg/kg and 60 mg/kg once daily. Control groups were given the same volume of saline. After the treatment with SPJ or saline for six months, the cortex and hippocampus were rapidly harvested and deposited at -80°C after the rats were decapitated under anesthesia. The neuroprotective effects of SPJ were estimated by histopathological observation, TUNEL detection, biochemical determination and western blotting.RESULTS:SPJ improved pathomorphological changes in neuronal cells and decreased apoptosis in the cortex and hippocampus of aging rats, increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na+/K+-ATPase, Ca2+-ATPase and Ca2+/Mg2+-ATPase whereas, decreased malondialdehyde (MDA) contents in the cortex of aging rats. Furthermore, the SPJ increased silent mating type information regulation 2 homolog-1 (SIRT1) protein expression, decreased acetylated level of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the cortex and hippocampus of aging rats, and reversed the aging-induced decline of Forkhead box O3 (Foxo3a), Superoxide Dismutase 2 (SOD2), microtubule-associated protein light chain 3 (LC3II) and Beclin1 levels in the cortex and hippocampus.CONCLUSION:Our data showed that SPJ conferred neuroprotection partly through the regulation of oxidative stress and mitochondria-related pathways in aging rats.

Sertoli cells play crucial roles in spermatogenesis and are impaired by aging. Icariin, a flavonoid from Epimedium, has been reported to exhibit anti-aging effects and improve testicular dysfunction in the clinical setting. However, whether icariin improves age-related degeneration of testicular function via protection from Sertoli cell injury remains unclear. In the present study, we evaluated the protective effect of icariin on Sertoli cell injury and explored the possible mechanism(s) in vivo and in vitro. Dietary administration of icariin for 4 months significantly ameliorated the age-related decline in testicular function by increasing testicular and epididymal weights and indices, sperm count and sperm viability, testicular testosterone and estradiol concentrations, and seminiferous tubule diameters and heights. In addition, icariin protected age-related Sertoli cells from injury as evidenced by an analysis of Sertoli cell number, ultrastructure, and function. Such changes were accompanied by upregulation of ERα and Nrf2 signaling in Sertoli cells. Parallel in vitro studies also demonstrated that icariin inhibited untoward effects on the TM4 mouse Sertoli cell line with concomitant upregulation of ERα and Nrf2 signaling. Conversely, ERα siRNA reversed icariin-mediated protection of Sertoli cell injury. Our data suggest that icariin effectively ameliorates age-related degeneration of testicular function by alleviating Sertoli cell injury via the ERα/Nrf2 signal-transduction pathway. Thus, mitigating Sertoli cell damage via the ERα/Nrf2 signaling pathway likely represents a promising strategy for the prevention of age-related testicular dysfunction.

Background and study aims: The renewal of intestinal epithelium is maintained by intestinal stem cells (ISCs). Studies have found an age-dependent increase of Esg(+)/Dl(+) progenitor cells in the midgut of Drosophila. However, changes of ISCs and the molecular regulation in mammalian animals with age are yet unknown. The aim of this study was to find out the changes of ISCs and molecular regulation in mammalian animals during the process of ageing. Material and methods: Thirty Sprague-Dawley rats were divided into three groups: young (3 months old), adult (6 months old), and ageing (24 months old). Levels of PCNA, Bmi1, beta-catenin and BMP4 were examined by Immunohistochemistry staining. Levels of Bmi1, GSK-3 beta, Dkk1 and BMP2 were determined by Western Blot. Results: Our results showed that the proliferation of ISCs was decreased and the number of intestinal stem cells declined in ageing rats. The niches of ISCs, including Wnt signalling pathway and some proteins of Bone morphogenetic protein (BMP) signalling pathway, were downregulated in the jejunum of ageing rats. Conclusion: Our study indicated that age-related decreased proliferation of intestinal stem cells in the jejunum could be associated with the alleviation of niches, including Wnt signalling pathway and some proteins of BMP signalling pathway. (C) 2019 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

机体累积过量的活性氧自由基所导致的氧化应激是多种肠道疾病发生的共同病理生理基础.肠上皮细胞间的紧密连接是维持肠屏障功能的重要结构基础之一.近年来研究表明,氧化应激能通过多种途径破坏肠上皮细胞间的紧密连接,导致肠上皮屏障功能障碍.本文对蛋白激酶C、丝裂原活化蛋白激酶、蛋白质的修饰以及缺氧诱导因子-1(HIF-1)在肠屏障功能障碍中的作用机制进行简要概述,旨在为肠屏障功能障碍的治疗和预后提供新的思路.

AimThe enteric nervous system degenerates gradually with age, and α‐synuclein (α‐syn) is a suitable marker of enteric nervous system degeneration, which is intimately related with endoplasmic reticulum stress and unfolded protein response (UPRER). Saponins from Panax japonicus (SPJ) have obvious protective effects on neurons in several degenerative disease models. Here, the study was designed to investigate whether SPJ could reverse the neuron degeneration through regulating the UPRER in the colon myenteric plexus of aging rats.MethodsAging rats had been treated with SPJ for 6 months since they were aged 18 months. Then, the colon samples were collected and neuron morphology in the myenteric plexus was observed. Immunohistochemistry staining was used to detect the expressions of NeuN, α‐syn, GRP78 and three different UPRER branches. Double immunofluorescence was used to determine the co‐localization of α‐syn and NeuN, GRP78 and NeuN.ResultsNeurons degenerated in the colon myenteric plexus of aging rats, but co‐localization of α‐syn and NeuN increased. In addition, both the expressions of GRP78 and three UPRER branch signaling pathway proteins decreased in the colon myenteric plexus of aging rats. Treatment of SPJ almost alleviated the above effects in aging rats, except for ATF6.ConclusionsSPJ could reverse the neuron loss caused by accumulation of α‐syn in the myenteric plexus of colon in aging rats, which is potentially associated with increased GRP78 and most URPER changes. Geriatr Gerontol Int 2021; 21: 85–93.