Diabetes mellitus (DM) is one of the major chronic diseases endangering human health worldwide, and disorders of hepatic glucose metabolism are its main feature. Glucose homeostasis is maintained by hepatic glycogen synthesis and catabolism, glycolysis, and gluconeogenesis. Inflammation can inhibit glycogen synthesis and cause persistent hyperglycemia via the c-Jun N-terminal kinase (JNK) signaling pathway. Shengdihuang Xiyangshen Zhimu Cangzhu (SXZC) formula is a botanical medicine complex with hypoglycemic effects, and it is not clear whether the SXZC formula could improve glucose metabolism in the liver. In this study, we are aimed at investigating the effect of the SXZC formula on hepatic glucose metabolism. The SXZC formula was administered to db/db mice for 4 weeks. Three concentration gradients of the SXZC formula were administered: a high-dose group (5.96 g·kg-1·d-1), a medium-dose group (2.98 g·kg-1·d-1), and a low-dose group (1.49 g·kg-1·d-1). The potential signaling pathways were identified by network pharmacology, subsequently validated via molecular docking and kinetic simulations, as well as molecular experiments. It was found that the SXZC formula reduced blood glucose levels, inflammatory and phosphorylation levels of JNK, c-Jun, and insulin receptor substrate 1 (IRS1), and promoted glycogen synthase kinase-3 β (GSK3β) phosphorylation and hepatic glycogen synthesis. We indicated that the SXZC formula alleviates hepatic inflammation and promotes hepatic glycogen synthesis by the JNK/c-Jun/IRS1/GSK3β signaling pathway.

Based on the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway, this study observed the regulatory effect of ginsenoside Rb_1(Rb_1) on liver lipid metabolism in db/db obese mice and explored its potential mechanism. Thirty 6-week-old male db/db mice were randomly divided into a model group, a metformin group, and Rb_1 groups with low, medium, and high doses, with six mice in each group. Additionally, six age-matched male db/m mice were assigned to the normal group. The intervention lasted for five weeks. Body weight, fasting blood glucose, and food intake were mea-sured weekly. At the end of the experiment, serum lipid levels and liver function were detected. Hematoxylin-eosin(HE) staining and oil red O staining were performed to observe pathological changes in liver tissue. Real-time quantitative PCR and immunohistochemistry on paraffin sections were used to detect the mRNA and protein expression of TLR4, MyD88, and NF-κB p65. RESULTS:: showed that compared with the normal group, the model group exhibited significant increases in body weight, liver weight, liver index, epididymal fat mass, epididymal fat index, total cholesterol, low-density lipoprotein cholesterol, liver function parameters, and fasting blood glucose levels. Liver lipid accumulation significantly increased, along with elevated mRNA and protein expression of TLR4, MyD88, and NF-κB p65 in the liver. After Rb_1 treatment, the above-mentioned parameters in the intervention groups showed significant reversals. In conclusion, Rb_1 can improve obesity and obesity-related hepatic steatosis in mice while regulating abnormal lipid and glucose meta-bolism. Mechanistically, Rb_1 may improve liver steatosis in db/db obese mice by modulating the TLR4/MyD88/NF-κB signaling pathway.

目的 定量分析体检人群肝脂肪变性与中医体质、BMI及实验室代谢指标的关系.方法 使用定量CT(quantitative computerized tomography,QCT)测量肝脏脂肪体积百分比(Fat％QCT),纳入肝脂肪变性程度≥5％的体检受试者158例.收集临床资料及中医体质结果,分析受试者的中医体质分布特点,观察Fat％QCT与中医体质、BMI及实验室代谢指标的相关性.结果 158例受试者的平均Fat％QCT为10.3±6.8％;肥胖组Fat％QcT值显著高于未超重组(11.7±4.1％VS 8.9±6.5％),糖尿病组Fat％QQCT值显著高于血糖正常组(14.2±11.4％VS 9.7±6.2％),两组组内均具有统计学意义.在中医体质方面,158例受试者中兼杂偏颇体质共124例(78.5％),前3位分别是痰湿质+湿热质、气虚质+痰湿质和气虚质+湿热质;单纯体质31例(19.6％),前3位分别是气虚质、湿热质和痰湿质.相关分析显示:受试者Fat％QCT与BMI、血糖及痰湿质显著正相关(rs=0.35、0.30、0.18,P＜0.05).结论 定量CT可以稳定评估脂肪肝,Fat％QCT值与BMI、血糖和中医体质相关.

Ampelopsis grossedentata is a flavonoid-rich healthy tea, traditionally used as a Chinese herbal medicine, that effectively treats T2DM. In the present study, we investigated the anti-diabetic effect of total flavonoids extracted from Ampelopsis grossedentata (AGT) and the underlying mechanisms using 16S rDNA sequencing and metabolomics. The results indicated that after AGT treatment for 6 weeks, the body weight, liver index, fasting blood glucose (FBG), OGTT-AUC, and serum lipid levels were reduced, and pathological injuries of the liver improved significantly in ZDF rats. Meanwhile, AGT increased the abundance and diversity of gut microbiota, especially BSH-active bacteria, which reduced T-beta-MCA and T-alpha-MCA levels and further activate FXR and FGF15. The activation of FXR-FGF15 axis inhibited excessive bile acid accumulation and liver gluconeogenesis upon AGT treatment. Taken together, our results suggested that AGT ameliorated glycolipid metabolism disorder via the "microbiota-gut-liver" axis, indicating that AGT may be a potential therapeutic strategy for treating T2DM.

Alzheimer's Disease (AD) is a global chronic disease in adults with beta-amyloid (Aβ) deposits and hyperphosphorylated tau protein as the pathologic characteristics. Although the exact etiology of AD is still not fully elucidated, aberrant metabolism including insulin signaling and mitochondria dysfunction plays an important role in the development of AD. Binding to insulin receptor substrates, insulin can transport through the blood-brain barrier (BBB), thus mediating insulin signaling pathways to regulate physiological functions. Impaired insulin signaling pathways, including PI3K/Akt/GSK3β and MAPK pathways, could cause damage to the brain in the pathogenesis of AD. Mitochondrial dysfunction and overexpression of TXNIP could also be causative links between AD and DM. Some antidiabetic medicines may have benefits in the treatment of AD. Metformin can be beneficial for cognition improvement in AD patients, although results from clinical trials were inconsistent. Exendin-4 may affect AD in animal models but there is a lack of clinical trials. Liraglutide and dulaglutide could also benefit AD patients in adequate clinical studies but not semaglutide. Dipeptidyl peptidase IV inhibitors (DPP4is) such as saxagliptin, vildagliptin, linagliptin, and sitagliptin could boost cognitive function in animal models. And SGLT2 inhibitors such as empagliflozin and dapagliflozin were also considerably protective against new-onset dementia in T2DM patients. Insulin therapy is a promising therapy but some studies indicated that it may increase the risk of AD. Herbal medicines are helpful for cognitive function and neuroprotection in the brain. For example, polyphenols, alkaloids, glycosides, and flavonoids have protective benefits in cognition function and glucose metabolism. Focusing on glucose metabolism, we summarized the pharmacological mechanism of hypoglycemic drugs and herbal medicines. New treatment approaches including antidiabetic synthesized drugs and herbal medicines would be provided to patients with AD. More clinical trials are needed to produce definite evidence for the effectiveness of hypoglycemic medications.

糖尿病引发的认知功能障碍被认为是引发痴呆的严重病因之一。目前糖尿病认知障碍的发病机制尚未完全清楚，西医对于该病的治疗效果尚无确切报道。中医学对该病病因病机及治疗具有独到见解，认为糖尿病认知障碍是从消渴病发展而来，饮食不节、外感六淫、情志内伤均可导致疾病的发生，以消渴病气阴两虚为基本病机，糖毒损脑络、散膏燥害、五脏亏损等病机与疾病的发生、发展关系密切，病位涉及脾、肾、脑。中药汤剂、中成药及针灸治法在疾病治疗上初见成效，但仍存在未形成专家共识、临床试验设计不合理及机制研究少等问题。

目的 观察清热泄浊方联合苯溴马隆治疗无症状高尿酸血症(Hyperuricemia,HUA)湿热证疗效及对血清炎性因子的影响.方法 选取2018年4月—2019年4月期间北京中医药大学东方医院收治的无症状HUA患者82例,分为对照组40例和治疗组42例,对照组脱落病例1例.两组患者均给予碳酸氢钠治疗,对照组加用苯溴马隆治疗,治疗组在对照组基础上加用清热泄浊方治疗.治疗4周后,观察比较两组患者临床疗效、不良反应,治疗前后中医证候积分、血尿酸水平、血清炎性因子[肿瘤坏死因子α(Tumor necrosis factorα,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-8(Interleukin-8,IL-8)]水平.结果 治疗后治疗组总有效率85.71％(36/42)明显高于对照组66.67％(26/39),差异有统计学意义(P<0.05).治疗后两组患者中医证候积分均较治疗前降低,差异有统计学意义(P<0.05);且治疗组中医证候积分明显低于对照组,差异有统计学意义(P<0.05).治疗后两组患者血尿酸水平均较治疗前降低,差异有统计学意义(P<0.05);且治疗组血尿酸水平明显低于对照组,差异有统计学意义(P<0.05).治疗后两组患者血清IL-6、IL-8及TNF-α水平均较治疗前降低,差异有统计学意义(P<0.05);且治疗组血清IL-6、IL-8及TNF-α水平均明显低于对照组,差异有统计学意义(P<0.05).两组患者治疗过程中均未出现药物相关不良反应.结论 清热泄浊方联合碳酸氢钠治疗无症状HUA的疗效显著,能有效改善临床症状,降低血尿酸及血清炎性因子水平,且安全性可靠,值得临床推广使用.

目的 讨论糖尿病在共同照护门诊模式下中西医结合管理的疗效评价以及用药情况分析.方法 选取在2018年5月—2021年1月21日期间就诊于北京中医药大学东方医院共同照护门诊的患者为研究对象,评估代谢指标改善情况、达标率及用药变化情况等.结果 共同照护门诊管理的患者总数为354例,初诊患者总数为290例,至少有一次复诊的患者数为234例(66.1％);初诊与最近一次复诊的数据相比,患者的代谢指标改善,其中糖化血红蛋白由(7.6±1.38)％降到(7.1±1.14)％,低密度脂蛋白由(2.8±0.74)mmol/L降到(2.7±0.82)mmol/L,糖化血红蛋白达标率由34.2％提升到54.3％,3B(血糖、血压、血脂)综合达标率由2.6％提升至9.4％,差异具有统计学意义(P<0.05);用药情况方面,初诊时未使用及仅使用一种降糖西物治疗的患者比例下降,使用两种降糖西药、三种及以上降糖西药、胰岛素以及使用中成药、中草药的患者比例提高,尤其是使用中成药来延缓慢性并发症的比例大幅度提高.结论 共同照护模式下的糖尿病中西医结合管理显著改善糖尿病患者代谢指标以及远期预后.

Objective: To explore the effects and dose–response relationship of Tai Chi for type 2 diabetes mellitus (T2DM) and to evaluate the methodological quality of the included trials and evidence quality of the outcomes. Methods: Nine major English and Chinese databases were searched for randomized controlled trials of Tai Chi for T2DM from inception to December 2021. The effects and dose–response relationships were assessed with a meta-analysis and meta-regression using Stata.16. The methodological quality of the included studies was assessed using the risk of bias tool. The evidence quality of the outcomes was assessed using the GRADE tool. Results: A total of 24 studies with 1314 patients were included. Compared with the usual care, Tai Chi improved HbA1c (MD = −0.80%, 95% CI [−1.05, −0.54], P < .001, I2 = 18.29%, very low–quality evidence), FBG (SMD = −0.58, 95% CI [−0.86, −0.31], P < .001, I2 = 53.2%, low-quality evidence), fasting insulin (FIN), diastolic blood pressure, BMI, and the outcomes of quality of life (QoL) in patients with T2DM. However, when Tai Chi was compared with other exercise, there was no between-group difference in the HbA1c, FBG, TC, TG, HDL, LDL, BMI, and waist circumference (WC). Furthermore, the findings showed that an increase at every 18 weeks in length or an 823-h increase in the total time of Tai Chi intervention resulted in approximately a one unit reduction in the SMD of FBG. Conclusion: Compared with usual care, Tai Chi may improve HbA1c (with clinical significance), FBG, FIN, BMI, diastolic blood pressure, and outcomes of QoL in T2DM patients. The effects of Tai Chi were similar to those of other exercises on the HbA1c, FBG, TC, TG, HDL, LDL, BMI, and WC. Given the overall poor methodological quality and evidence quality, these findings should be treated cautiously.

目的 分析2型糖尿病(T2DM)患者中医证型的分布特点,探讨其主要证型中患者体重指数与兼证的相关性.方法 回顾性收集1400例T2DM患者相关资料,符合研究标准者共470例.将470例T2DM患者的临床资料依据临床症状及四诊信息进行辨证分型,主要证型包括热盛伤津证、阴虚燥热证、气阴两虚证和阴阳两虚证;兼证包括气滞证、痰湿证、湿热证、血瘀证.将其中主要证型患者按照肥胖诊断标准分为体重正常组、超重组和肥胖组,分析3组患者一般资料、实验室指标[包括年龄、性别、病史、体重指数(BMI)、收缩压(SBP)、舒张压(DBP)、空腹血糖(FPG)、空腹C肽(C-Peptide)、糖化血红蛋白(HbA1c)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)]及兼证分布情况,并采用Logistic回归方法对T2DM主要证型患者超重和肥胖的影响因素进行分析.结果 470例T2DM患者中热盛伤津证32例(6.81％)、阴虚燥热证56例(11.92％)、气阴两虚证359例(76.38％)、阴阳两虚证23例(4.89％),提示气阴两虚证为主要证型.359例气阴两虚型T2DM患者中体重正常组116例,超重组122例,肥胖组121例.肥胖组患者的C-Peptide明显低于体重正常组,差异具有统计学意义(P＜0.05);各组患者年龄、性别、病程、SBP、DBP、FPG、HbA1c、HDL、LDL组间差异均无统计学意义(P＞0.05).体重正常组的兼证以血瘀为主,超重组和肥胖组以痰湿、湿热为主;对气阴两虚型T2DM超重和肥胖患者而言,C-Peptide(P＜0.05,β＝-0.26＜0,OR = 0.77＜1)是保护因素,痰湿是危险因素(P＜0.05,3 =1.39＞0,OR =4.01＞1),血瘀(P＜0.05,β=-3.06＜0,OR=0.047＜1)较少见.结论 在T2DM进展过程中,气阴两虚证为主要证型;体重正常的患者兼证以血瘀为主,超重和肥胖的患者兼证以痰湿、湿热为主.在T2DM治疗过程中,对超重或者肥胖的T2DM患者,在益气养阴的同时应重视健脾祛湿化痰;对体重正常的T2DM患者,在益气养阴的同时应注重活血化瘀.

重镇潜阳药物是临床常用的药物,但金石之性猛烈,使用不慎容易伤人,所以使用时须结合患者全身气血阴阳之虚实强弱,同时配合益阴、温阳等法,整体辨证、综合配伍才能充分发挥其功效.文章通过对常用重镇类药物的整理研究,结合古今医家经典论述,总结出平肝潜阳、益阴潜阳、镇心安神、降逆止呕、下气平喘、坠痰降浊、制衡升药7种用法,并参考经典配伍,分别阐明主要药物及治法的应用要点、配伍规律与禁忌,以期为临床合理使用重镇类药物提供参考.

Objective: The pancreatic endocrinal system dominates the regulation of blood glucose levels in vivo, and the dysfunction of pancreatic endocrine β-cells is a major cause of the occurrence and development of Type 2 diabetes (T2D). Although microRNA (miRNA) have been found to be key regulators of pancreatic β-cells proliferation, differentiation and apoptosis, the underlying mechanism remains enigmatic. The aim of this study was to identify several novel miRNAs which might be involved in the etiopathogenesis of diabetic β-cells dysfunction. Methods: The miRNA expression profiles in the pancreas of high-fat diet (HFD) fed Zucker diabetic fatty (ZDF) rats and Zucker lean (ZL) rats feed with normal-fat diet (NFD) were detected by using miRNA microarray chip, and individually verified the most significant factors by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to predict the target genes related to each of the identified miRNAs and the functions of these target genes in different metabolic signaling pathways. Results: Compared with the ZL rats, a total of 24 differentially expressed miRNAs were detected in ZDF rats. Among which miR-34a-5p and miR-452-5p were the most significantly up-regulated and down-regulated respectively. These miRNAs have not been reported in rats' pancreas before. By GO and KEGG enrichment analyses, we found that miR-34a-5p could negatively regulate pancreatic β-cell proliferation through the involvement of Wnt signaling pathway. In addition, it was also found to regulate insulin secretion through the insulin signaling pathway to modulate blood glucose levels. At the same time, miR-452-5p was found to positively regulate the activity of the key rate-limiting enzyme branched-chain α-keto acid dehydrogenase-β (BCKDHB) in the catabolism of branched chain amino acids (BCAA), leading to mitochondrial dysfunction in pancreatic β-cells. Conclusions: miR-34a-5p and miR-452-5p were identified as the novel regulators of pancreatic endocrine dysfunction. These miRNAs might have the potential to be utilized as the new predictive biomarkers for the diagnosis of the occurrence and development of T2D, as well as the therapeutic targets for T2D treatment.

目的 运用病例对照研究探讨中医药治疗与糖尿病视网膜病变发生的相关性,为该病的防治提供依据.方法 应用病例对照研究设计,在北京4家医院收集研究对象,以2型糖尿病合并视网膜病变的患者为病例组,以2型糖尿病不合并视网膜病变的患者为对照组,病例与对照以1:4的比例按照年龄、性别匹配研究对象.自行设计调查问卷,采用一对一调查的方式收集资料,应用Epi-Data 3.1软件录入数据,采用条件logistic回归的方法,应用SPSS 22.0软件分析中医药(治疗糖尿病或相关并发症为目的)与糖尿病视网膜病变患病的相关性.结果 病例组共纳入72例2型糖尿病合并视网膜病变的患者,对照组纳入236例2型糖尿病患者.病例组男性36人、女性36人,平均年龄(62.3±10.0)岁,病程[13(6,19)]年;对照组男性112人、女性124人,平均年龄(61.5±9.6)岁,病程[10(5,15)]年.单因素条件logistic回归分析显示病例组与对照组既往接受中医药治疗比例分别为52.8％和33.5％,差异有统计学意义(OR=2.505,95％CI:1.412-4.443).调整病程后,多因素条件logistic回归分析显示病例组与对照组既往接受中医药治疗比例差异有统计学意义(OR=2.296,95％CI:1.269-4.156).结论 中医药治疗与2型糖尿病患者是否合并视网膜病变具有相关性,有糖尿病视网膜病变的患者接受过中医药治疗的比例高且中医药治疗的平均时间较长,但鉴于病例对照研究的局限性,尚需要进一步前瞻性的研究设计结果加以证实.

β细胞的功能缺陷是我国2型糖尿病的主要的发病机制之一.近年来大量研究表明β细胞去分化是β细胞功能缺陷的主要原因,而FOXO1是对β细胞的去分化有着重要影响的核转录因子,这方面的研究可以为糖尿病的治疗和研究提供新的思路和方向.本文针对FOXO1影响β细胞去分化的作用机制,以及能够抑制和逆转β细胞去分化的干预措施做了系统的总结和分析,发现减肥和饮食控制,以及早期使用胰岛素被证明可以有效抑制和逆转β细胞去分化,其他药物在此方面的作用尚需要进一步证实.

目的:探究番石榴叶提取物调节脂肪细胞分化的作用机制.方法:6周龄雄性SPF级db/db小鼠24只、同龄C57BL/6J正常组小鼠6只,将符合纳入标准的db/db小鼠根据体重、血糖随机分为模型组和番石榴叶提取物高剂量组、番石榴叶提取物中剂量组、番石榴叶提取物低剂量组,并将番石榴叶提取物按高、中、低剂量进行灌胃,于4周后空腹脱臼处死所有小鼠,分别取后腿腓肠肌组织、皮下脂肪组织进行原代成肌细胞、原代脂肪组织SVF细胞的培养、接种和传代.培养48 h后收集细胞并提取蛋白,Western blot法检测各组成肌细胞PGC-1α、FNDC5蛋白和各组脂肪组织SVF细胞Prdm16蛋白的表达.结果:第4周时,与模型组小鼠相比,番石榴叶提取物高剂量组小鼠体重、血糖、低密度脂蛋白降低(均P<0.05).番石榴叶提取物高剂量组小鼠成肌细胞PGC-1α、FNDC5蛋白表达升高,脂肪组织SVF细胞Prdm16蛋白表达较模型组升高(均P<0.05).结论:番石榴叶提取物高剂量可通过促进白色脂肪细胞向棕色脂肪细胞分化,提高棕色脂肪水平,从而通过增加机体的能量代谢来调节脂质代谢.

AIMS:Diabetic kidney disease (DKD) is a major prevalent chronic microvascular complication of type 2 diabetes (T2D). However, the present diagnostic indicators have limitations in the early diagnosis of DKD. This study concentrated on the sensitive and specific biomarkers in early diagnosis of DKD by metabolomics.MATERIALS AND METHODS:In this cross-sectional study, we performed a UPLC-MS based nontargeted metabolomics assay to profile the urinary metabolites in patients with DKD. Principal Component Analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA) were used for screening out the metabolomic variables.KEY FINDINGS:A total of 147 urinary metabolites were identified and 5 metabolic pathways were correlated with DKD pathophysiology. Pantothenate and coenzyme A biosynthesis pathway alteration was found the most prominent in DKD subjects. 4 metabolites, including dihydrouracil, ureidopropionic acid, pantothenic acid (PA), and adenosine 3',5'-diphosphate involved in pantothenate and CoA biosynthesis were significantly down-regulated.SIGNIFICANCE:Our finding indicates that PA would be served as a novel predictive biomarker associated with DKD development and progression. Furthermore, our results provide a promising prospect that PA and CoA biosynthesis pathway can be potential therapeutic targets for DKD treatment.

自身免疫性甲状腺炎是最常见的甲状腺疾病之一,近年来患病率不断上升.现代医学尚无针对其病因的治疗方法,以对症治疗为主,疗效有限,并有一定的副作用.中医药通过多靶点、协同增效,改善各脏腑功能,调节自身免疫以降低甲状腺抗体滴度水平、减轻病理损伤来控制病情进展.同时可以纠正异常的甲功,有效改善患者的症状,提高生活质量.深入研究自身免疫性甲状腺炎的中医药治疗具有重要的临床价值及社会意义.刘铜华教授在长期的临床和科研工作中对于本病有着深刻的理解:认为本病多起于情志内伤,以气郁为先导,痰凝、瘀阻贯穿疾病始终,气、痰、瘀滞颈前而为病.治以理气解郁、化痰祛瘀、消瘿散结.同时防治结合,既病防变,兼顾正气.在此基础上创立了疗效确切的经验方甲炎康泰方.传承疗效确切的临床经验和学术思想并不断创新,能够有力推动中医药的发展.本文对刘铜华教授治疗自身免疫性甲状腺炎的临床经验进行论述总结.

目的:探究辣木叶醇提物对ZDF大鼠肝脏肝X受体α(LXR-α)/维甲酸受体(RXR)信号通路及固醇原件调节蛋白1c(SREBP-1c)蛋白表达的影响.方法:雄性已诱导的高血糖ZDF(fa/fa)大鼠24只随机分为模型组、低剂量组、高剂量组,每组8只,同窝ZL对照8只为正常组.高、低剂量组予600、300mg/kg辣木叶醇提物水溶液灌胃,其余两组大鼠予等量0.9％氯化钠溶液灌胃.干预6周后处死大鼠,留取血清检测血糖、血脂、游离脂肪酸,肝脏组织-80℃冻存,RT-PCR检测大鼠肝脏LXR-α、RXR、SREBP-1c mRNA转录情况,蛋白印迹法检测大鼠肝脏SREBP-1c蛋白表达情况.结果:低、高剂量组大鼠血糖、体质量、总胆固醇(CHO)、空腹胰岛素水平、HOMA-IR均显著低于模型组(P＜0.05,P＜0.01);低剂量组甘油三酯(TG)水平低于模型组(P<0.05),高剂量组游离脂肪酸水平低于模型组(P＜0.05);与模型组比较,高、低剂量组肝脏LXR-α、RXR、SREBP-1c基因转录显著降低(P＜0.05),肝脏SREBP-1c蛋白表达下降(P＜0.01).结论:辣木叶醇提物能显著改善ZDF大鼠糖脂代谢,其机制可能与改善肝脏胰岛素抵抗,下调LXR-α/RXR信号通路,降低SREBP-1c蛋白表达相关.

目的:探讨番石榴叶提取物对糖尿病db/db小鼠骨骼肌AMPK-PGC-1α-FNDC5信号通路的影响.方法:实验共纳入24只6周龄雄性db/db小鼠及6只同龄雄性C57BL/6J小鼠,适应性喂养两周后,6只C57BL/6J雄性小鼠作为正常组,db/db小鼠检测空腹血糖≥7.0 mmol/l者视为造模成功,并随机分为模型组和番石榴叶提取物高、中、低剂量组,每组各6只.番石榴叶提取物按高剂量14 mg/kg、中剂量7 mg/kg、低剂量3.5 mg/kg每日进行灌胃,正常组小鼠灌服等量蒸馏水,干预4周.每周监测小鼠进食量、体重和空腹血糖.实验结束后,将小鼠空腹脱臼处死,并从眼眶取血,测定血浆胰岛素水平.Western-blot检测AM PK-α、p-AM PK-α、PGC-1α、FNDC5蛋白在骨骼肌中的表达,以及PGC-1α、UCP-1在脂肪组织中的表达.结果:番石榴叶提取物高剂量组小鼠相比模型组小鼠体重、血糖均显著降低,中剂量组小鼠在第2周血糖也出现明显下降,高、中剂量组小鼠的胰岛素水平均降低.检测蛋白表达结果显示,番石榴叶提取物干预的小鼠骨骼肌P-AM PK-α、PGC-1α、FNDC5蛋白和脂肪组织PGC-1α、UCP-1蛋白的表达均明显高于模型组.结论:番石榴叶提取物可通过增强骨骼肌的AM PK-PGC-1α-FNDC5信号通路传导,诱导白色脂肪组织棕色化,以实现降低血糖、减轻体重.

辣木叶是印度传统草药,现代医学研究证明,辣木叶可以治疗高血压病、糖尿病、高脂血症、肝肾功能异常、肥胖、癌症、癫痫、老年痴呆等多种疾病,是一种具有极高的药用价值且价位低廉的植物药,对其药性研究有利于扩大辣木叶的适用范围,更好地挖掘其药用价值.根据现有的研究,结合中医性味归经理论,推测辣木叶性寒凉,味甘、苦,性沉降,归肝、脾(或/及胃)经,属安全剂量下的无毒类药材,其配伍及禁忌尚不明,功效为健脾化痰除湿、清肝泻火,可用于治疗肝火上炎的甲亢、肝阳上亢及痰湿中阻的高血压病、脾虚痰湿的肥胖症及糖尿病等.借助实验室手段,可以更加客观地评估辣木叶的中药药性,以促进海外植物药辣木叶的"中药化",拓展中药新资源.