Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus

Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.

Glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes:A new horizon

Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.

A Retrospective Analysis of Glucagon-Like Peptide 1 Receptor Agonists in Treating Type 2 Diabetes Mellitus Complicated by Nonalcoholic Fatty Liver Disease

Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.

Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease:Opportunities and challenges

Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 diabetes.Due to the growing global health burden and com-plex pathogenesis of MASLD,a multifaceted and innovative therapeutic approach is needed.Incretin receptor agonists,which were initially developed for diabetes management,have emerged as promising candidates for MASLD treatment.This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists:glucagon-like peptide-1 receptor agonists,glucose-dependent insulinotropic polypeptide receptor agonists,and glucagon receptor agonists.Incretins and glucagon directly or indirectly impact various organs,including the liver,brain,pancreas,gastro-intestinal tract,and adipose tissue.Thus,these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis.Importantly,this study provides a summary of clinical trials analyzing the effect-iveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function,hepatic steatosis,and intrahepatic inflammation.There are emerging challenges associated with the use of these medications in the real world,particularly adverse events,drug-drug interactions,and barriers to access,which are discussed in detail.Additionally,this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.

Effects of glucagon-like peptide-1 receptor agonists on glucose excursion and inflammation in overweight or obese type 2 diabetic patients

BACKGROUND Currently,the lack of comparative studies between weekly and daily formulations of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for glucose excursion is worth investigation.AIM To investigate the effects of weekly and daily formulations of GLP-1RA on glucose excursion and inflammation in overweight and obese patients with type 2 diabetes.METHODS Seventy patients with type 2 diabetes mellitus who were treated at our hospital between January 2019 and January 2022 were enrolled in this retrospective analysis.All patients were treated with metformin.We evaluated changes in blood glucose levels and a series of important indicators in patients before and after treatment with either a weekly or daily preparation of GLP-1RA(group A;n=33 and group B;n=37).RESULTS The degree of decrease in the levels of fasting blood glucose,mean blood glucose,mean amplitude of glycemic excursions,total cholesterol,triglycerides,tumor necrosis factor-α,interleukin-6,and high-sensitivity C-reactive protein after treatment in group A was higher than that in group B(P<0.05),whereas the 2-h postprandial blood glucose levels decreased more so in group B than in group A(P<0.001).However,there were no statistically significant differences in the levels of glycated hemoglobin,standard deviation of blood glucose,coefficient of variation,absolute mean of daily differences,percentage of time with 3.9 mmol/L<glucose<10 mmol/L,and high-and low-density lipoproteins between the two groups(P>0.05).The incidence of adverse reactions was significantly lower in group A than in group B(P<0.05).CONCLUSION The effect of the weekly preparation of GLP-1RA in controlling blood glucose levels in the patients,suppressing inflammation,and reducing adverse reactions was significantly higher than that of the daily preparations,which is worthy of clinical promotion.

达格列净联合胰高血糖素样肽-1受体激动剂对2型糖尿病的疗效研究

目的探讨达格列净联合胰高血糖素样肽-1受体激动剂(GLP-1 RAs)对2型糖尿病患者血液流变学及胰岛素抵抗的影响。方法将2020年11月—2022年10月泉州市中医院收治的102例2型糖尿病患者随机分为2组,每组51例。对照组给予达格列净治疗,研究组采用达格列净联合GLP-1 RAs(利拉鲁肽)的治疗方案。比较2组临床疗效、血糖指标[空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)]、空腹胰岛素(FINS)及胰岛素抵抗[胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)]、血脂指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、血液流变学指标[红细胞聚集指数(EAI)、红细胞压积(HCT)、红细胞变形指数(EDI)、血浆黏度(PV)]和不良反应。结果研究组总有效率为94.12%,高于对照组的80.39%,差异有统计学意义(P<0.05)。研究组和对照组治疗后FBG、2 hPG、HbAlc、BMI均低于治疗前,且研究组治疗后FBG、2 hPG、HbAlc水平低于对照组,差异有统计学意义(P<0.05)。治疗后,研究组FINS、HOMA-β水平高于对照组,HOMA-IR水平低于对照组,差异有统计学意义(P<0.05)。研究组和对照组治疗后HDL-C均高于治疗前,TC、TG、LDL-C水平均低于治疗前;研究组治疗后HDL-C水平高于对照组,TC、TG、LDL-C水平低于对照组,差异均有统计学意义(P<0.05)。治疗后,研究组和对照组EAI、HCT、EDI、PV水平均低于治疗前,且研究组EAI、HCT、EDI、PV水平低于对照组,差异均有统计学意义(P<0.05)。研究组不良反应总发生率为11.76%,与对照组的9.80%比较,差异无统计学意义(P>0.05)。结论达格列净联合GLP-1 RAs(利拉鲁肽)治疗2型糖尿病的疗效确切,可有效调节患者血糖及血脂水平,缓解胰岛素抵抗,改善血液流变学指标。

GLP-1受体激动剂药品评价体系构建与遴选实践

目的 基于《中国医疗机构药品评价与遴选快速指南(第二版)》(以下简称《快速指南》),对GLP-1受体激动剂进行综合评价,提高医院药事服务质量,为医院开展药品临床综合评价与遴选工作建立标准、合适、规范的参考依据和工作指导。方法 参考《快速指南》,从临床属性(有效性和安全性)、药学特性、经济性、其他属性4个维度对纳入的药品进行赋分,制定出符合医院实际的药品临床综合评价体系,开展评价并记录评价结果。结果 司美格鲁肽77.4分、利拉鲁肽76.6分、度拉糖肽73.9分、聚乙二醇洛塞那肽72.7分、利司那肽69.4分、艾塞那肽67.8分、贝那鲁肽65.5分。司美格鲁肽、利拉鲁肽、度拉糖肽、聚乙二醇洛塞那肽为强推荐,利司那肽、艾塞那肽、贝那鲁肽为弱推荐。结论 GLP-1受体激动剂是合并心血管疾病高危因素的糖尿病患者一线降糖药物之一,不同GLP-1受体激动剂在临床治疗中有不同的优势。通过《快速指南》对GLP-1受体激动剂进行遴选评价,可为医疗机构药品遴选与合理用药提供科学的参考依据。

金水宝联合胰高血糖素样肽-1受体激动剂治疗对糖尿病肾病患者肾功能、肾脏血流及血管内皮功能的影响

目的 探究金水宝联合胰高血糖素样肽-1受体激动剂(glucagon-likepeptide-1,LP-1)治疗对糖尿病肾病患者肾功能、肾脏血流及血管内皮功能的影响。方法 采用随机数字表法将2020年3月—2022年8月收治的96例糖尿病肾病患者分为观察组(n=48)与对照组(n=48)。对照组采用GLP-1受体激动剂,观察组在此基础上联合使用金水宝治疗。观察两组患者治疗前后中医证候积分、肾功能、肾脏血、氧化应激指标及血管内皮功能水平。观察两组患者临床疗效和不良反应发生率。结果 两组患者治疗前尿频、精神萎靡、口渴喜饮和易饥多食中医证候积分差异无统计学意义(P>0.05)。治疗后,观察组尿频、精神萎靡、口渴喜饮和易饥多食中医证候积分显著低于对照组(P<0.05)。两组患者治疗前24 h尿蛋白定量、同型半胱氨酸(homocysteine, Hcy)、尿白蛋白排泄率(urinary albumin excretion, UAER)、血清肌酐(serum creatinine, Scr)水平差异无统计学意义(P>0.05)。治疗后,观察组24 h尿蛋白定量、Hcy、UAER和Scr水平显著低于对照组(P<0.05)。两组患者治疗前段间动脉血流灌注指数(Perfusion Index, PI)、段间动脉胰岛素(Regular Insulin, RI)和叶间动脉RI水平差异无统计学意义(P>0.05)。治疗后,观察组段间动脉PI、段间动脉RI和叶间动脉RI水平显著低于对照组(P<0.05)。两组患者治疗前丙二醛(malondialdehyde;malonic dialdehyde, MDA)、脂质过氧化氢(lipid peroxidation, LPO)、谷胱甘肽过氧化物酶(glutathione Peroxidase, GPX)、总抗氧化能力(total antioxidative capability, T-AOC)水平差异无统计学意义(P>0.05)。治疗后,观察组MDA、LPO水平显著低于对照组,且GPX和T-AOC水平显著高于对照组(P<0.05)。观察组总有效率为89.58%(43/48)显著高于对照组72.92%(35/48)(χ^(2)=4.376,P=0.036)。观察组总不良反应发生率为8.32%(4/48),略低于对照组的10.42%(5/48),但差异无统计学意义(χ^(2)=0.123,P=0.726)。结论 金水宝联合GLP-1受体激动剂能有效提高临床疗效,改善肾功能和肾脏血流,促进血管内皮功能恢复。

GLP-1RAs在治疗非典型抗精神病药相关代谢紊乱中的研究进展

接受非典型抗精神病药物(Atypical antipsychotics, AAPs)治疗的精神障碍患者发生代谢紊乱的风险明显升高。然而,针对AAPs相关代谢紊乱的干预措施有限。近年来,胰高血糖素样肽-1受体激动剂(GLP-1RAs)的减重作用已在非糖尿病患者中得到认可,且此类药物用于治疗AAPs导致的代谢紊乱的研究也愈加广泛,这可能具有显著临床意义。本文主要对GLP-1RAs治疗AAPs相关代谢紊乱的研究进展进行综述。

胰高血糖素样肽-1受体激动剂在儿童患者中的临床应用进展

胰高血糖素样肽-1受体激动剂(GLP-1RA)在成人2型糖尿病的治疗中已有广泛应用,近年来的研究结果表明,GLP-1RA也可用于儿童肥胖和短肠综合征的治疗。本篇综述主要关注GLP-1RA在儿童患者中的临床应用进展。GLP-1RA通过改善胰岛素敏感性、减轻体重、降低血压和降低代谢综合征发生风险来改善儿童肥胖患者的代谢异常和心血管疾病风险。在短肠综合征中,GLP-1RA可增加肠道对养分的吸收,刺激胰岛素分泌,促进葡萄糖的利用和减少外源性葡萄糖的使用,增加脂肪的利用。GLP-1RA虽在临床应用中具有良好的安全性和耐受性,但也存在低血糖、恶心和呕吐、胰腺炎和甲状腺癌等风险,故需要密切监测患者的不良反应,进一步开展更加系统和深入的研究。

Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation

Glucagon-like peptide1(GLP-1)is secreted from Langerhans cells in response to oral nutrient intake.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are a new class of incretin-based anti-diabetic drugs.They function to stimulate insulin secretion while suppressing glucagon secretion.GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus(T2DM),and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases.As we know,along with change in lifestyles,the prevalence of non-alcoholic fatty liver disease(NAFLD)in China is rising more than that of viral hepatitis and alcoholic fatty liver disease,and NAFLD has become the most common chronic liver disease in recent years.Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels,cutting down the fatcontent to promote fat redistribution,directly decreasing fatty degeneration of the liver,reducing the degree of liver fibrosis and improving inflammation.This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials.

Effects of glucagon-like peptide-1 receptor agonists on renal function

Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of case reports show an association of GLP-1receptor agonists,mainly exenatide,with the development of acute kidney injury.The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function,their use in subjects with chronic renal failure and their possible association with acute kidney injury.Based on the current evidence,exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease.Liraglutide is not eliminated by renal or hepatic mechanisms,but it should be used with caution since there are only limited data in patients with renal or hepatic impairment.There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect.Additionally,there is evidence that GLP-1 receptor agonists influence water and electrolyte balance.These effects may represent new ways to improve or even prevent diabetic nephropathy.

Treatment of type 2 diabetes, lifestyle, GLP1 agonists and DPP4 inhibitors

In recent years the treatment focus for type 2 diabetes has shifted to prevention by lifestyle change and to more aggressive reduction of blood sugars during the early stage of treatment. Weight reduction is an important goal for many people with type 2 diabetes.Bariatric surgery is no longer considered a last resort treatment. Glucagon-like peptide-1 agonists given by injection are emerging as a useful treatment since they not only lower blood sugar but are associated with a modest weight reduction. The role of the oral dipeptidyl peptidase 4 inhibitors is emerging as second line treatment ahead of sulphonylureas due to a possible beneficial effect on the beta cell and weight neutrality.Drugs which inhibit glucose re-absorption in the kidney,sodium/glucose co-transport 2 inhibitors, may have a role in the treatment of diabetes. Insulin treatment still remains the cornerstone of treatment in many patients with type 2 diabetes.

Review on the Effect of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease（NAFLD） is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus（T2DM）, dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1（GLP-1） analogues and dipeptidyl peptidase-4（DPP-4） inhibitors were widely used to treat T2 DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor（GLP-1R） is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride（TG） content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and m RNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

Development of a New High-throughput Screening Model for Human High Density Lipoprotein Receptor (CLA-1) Agonists

To develop a new high-throughput screening model for human high-density lipoprotein （HDL） receptor （CD36 and LIMPⅡ analogous-1, CLA-1） agonists using CLA-1-expressing insect cells. Methods With the total RNA of human hepatoma cells BEL-7402 as template, the complementary DNA （cDNA） of CLA-1 was amplified by reverse transcription-polymerase chain reaction （RT-PCR）. Bac-to-Bac baculovirus expression system was used to express CLA-1 in insect cells. CLA-1 cDNA was cloned downstream of polyhedrin promoter of Autographa californica nuclear polyhedrosis virus （AcNPV） into donor vector pFastBacl and recombinant pFastBacl-CLA-1 was transformed into E. coli DH10Bac to transpose CLA-1 cDNA to bacrnid DNA. Recombinant bacrnid-CLA-1 was transfected into Spodopterafrugiperda Sf9 insect cells to produce recombinant baculovirus particles. Recombinant CLA- 1 was expressed on the membrane of Sf9 cells infected with the recombinant baculoviruses. A series of parameters of DiI-lipoprotein binding assays of CLA-1-expressing Sf9 cells in 96-well plates were optimized. Results Western blot analysis and DiI-lipoprotein binding assays confirmed that CLA-1 expressed in insect cells had similar immunoreactivity and ligand binding activity as its native counterpart. A reliable and sensitive in vitro cell-based assay was established to assess the activity of CLA-1 and used to screen agonists from different sample libraries. Conclusion Human HDL receptor CLA-1 was successfully expressed in Sf9 insect cells and a novel high-throughput screening model for CLA-1 agonists was developed. Utilization of this model allows us to identify potent and selective CLA-1 agonists which might possibly be used as therapeutics for atherosclerosis.

Glucagon-like peptide-1 receptor agonists favorably address all components of metabolic syndrome

Cardiovascular death is the leading cause of mortality for patients with type 2 diabetes mellitus. The etiologyof cardiovascular disease in diabetes may be divided into hyperglycemia per se and factors operating through components of metabolic syndrome(Met S). Hyperglycemia causes direct injury to vascular endothelium and possibly on cardiac myocytes. Met S is a cluster of risk factors like obesity, hyperglycemia, hypertension and dyslipidemia. The incidence of this syndrome is rising globally. Glucagon-like peptide-1 receptor agonists(GLP-1RA) are a group of drugs, which address all components of this syndrome favorably. Experimental evidence suggests that they have favorable actions on myocardium as well. Several compounds belonging to GLP-1RA class are in market now and a large number awaiting their entry. Although, originally this class of drugs emerged as a treatment for type 2 diabetes mellitus, more recent data generated revealed beneficial effects on multiple metabolic parameters. We have studied literature published between 2000 and 2016 to look into effects of GLP-1RA on components of Met S. Results from recently concluded clinical trials suggest that some of the molecules in this class may have favorable effects on cardiovascular outcome.

The Role for AVE0991 (MAS-Receptor Angiotensin II (1-7) Agonist) in Reducing Cisplatin-Induced Acute Kidney Injury on C57BL/6 Mice

Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.

Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus.This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant effects.On the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate.However,this might be due to the relatively short duration of the trials that evaluated their effects on DKD.Moreover,these trials were not designed nor powered to assess renal outcomes.Given than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term.Nevertheless,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.

Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

Non-alcoholic fatty liver disease(NAFLD)is the predominant cause of chronic liver disease worldwide.NAFLD progresses in some cases to non-alcoholic steatohepatitis(NASH),which is characterized,in addition to liver fat deposition,by hepatocyte ballooning,inflammation and liver fibrosis,and in some cases may lead to hepatocellular carcinoma.NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus(T2DM).Currently,lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are used in the management of T2DM and do not have major side effects like hypoglycemia.In patients with NAFLD,the GLP-1 receptor production is down-regulated.Recently,several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation,alleviating the inflammatory environment and preventing NAFLD progression to NASH.In this review,we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH.Finally,as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD,we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.

组胺H 1受体激动剂通过Akt/NF-κB通路抑制脂多糖诱导的星形胶质细胞炎症反应

目的探讨组胺H 1受体(histamine H 1 receptor,H 1R)对脂多糖(lipopolysaccharide,LPS)诱导的星形胶质细胞炎症反应的影响及其调控机制。方法采用LPS建立体外星形胶质细胞炎症模型,随机将大鼠原代星形胶质细胞分为对照组、LPS组、LPS+H 1R激动剂组(2-pyridylethlamine,Pyri)和H 1R激动剂组。对照组仅加入培养液,LPS+H 1R激动剂组提前在培养液中加入100μmol·L-1的Pyri,1 h后再加入终浓度为100μg·L-1的LPS。CCK-8法检测细胞活性;免疫荧光法检测活化标记物GFAP和H 1R的表达;倒置相差显微镜下观察星形胶质细胞的形态变化;ELISA法检测细胞上清中炎症因子TNF-α和IL-6水平;Western blot检测p-Akt、Akt、p-NF-κB p65、NF-κB p65的蛋白表达。结果与对照组比较,LPS组星形胶质细胞分支和辐射状突起减少,GFAP表达增加,细胞表面H 1R表达下调,上清液中TNF-α和IL-6含量增加,Akt和NF-κB p65的磷酸化水平明显增加;与LPS组相比,LPS+H 1R激动剂组激活态星形胶质细胞减少,GFAP表达降低,培养基上清中TNF-α和IL-6的含量明显下降,Akt和NF-κB p65的磷酸化表达明显降低。结论H 1R激动剂能够抑制LPS诱导的星形胶质细胞活化和炎症因子的表达,且Akt/NF-κB通路可能是H 1R参与星形胶质细胞免疫调节的重要途径。