依布硒啉对db/db小鼠蛋白尿作用及其机制

目的探讨依布硒啉（ebselen）对db/db小鼠蛋白尿的作用及其可能机制。方法 16只8周龄db/db小鼠随机分为依布硒啉组8只（Ebs组）和糖尿病肾病组8只（DN组）,分别给予依布硒啉50mg/kg和生理盐水灌胃,2次/d;8只8周龄db/m小鼠为非糖尿病对照组（对照组）,给予生理盐水灌胃,2次/d;每周监测各组体质量、空腹血糖。8周后检测24h尿白蛋白、尿8-羟基脱氧鸟苷酸、肾脏组织丙二醛含量、超氧化物歧化酶和谷胱甘肽过氧化物酶活性。结果治疗8周后,DN组空腹血糖（（31.9±2.4）mmol/L）、24h尿白蛋白（（240.7±26.3）μg/24h）、尿8-羟基脱氧鸟苷酸（183.5±26.7）ng/24h）、肾组织匀浆丙二醛含量（（11.5±2.2）nmol/mg）明显高于对照组（（6.7±0.8）mmol/L、（16.4±1.1）μg/24h、（74.8±13.5）ng/24h、（3.6±0.9）nmol/mg）和Ebs组（（21.3±1.1）mmol/L、（76.3±14.7）μg/24h、（86.9±16.5）ng/24h、（7.7±1.6）nmol/mg）,肾脏组织超氧化物歧化酶和谷胱甘肽过氧化物酶活性（（312.4±16.9）、（167.2±14.8）u/mg）明显低于对照组（（358.2±13.4）、（217.4±15.7）u/mg）和Ebs组（（366.5±24.7）、（191.2±16.5）u/mg）（P〈0.01）;Ebs组空腹血糖、24h尿白蛋白和肾组织丙二醛含量高于对照组（P〈0.01）,尿8-羟基脱氧鸟苷酸水平、超氧化物歧化酶和谷胱甘肽过氧化物酶活性与对照组比较差异无统计学意义（P〉0.05）。结论依布硒啉能降低蛋白尿,其机制可能与减轻db/db小鼠肾脏组织氧化应激有关。     

肝X受体激动剂对db/db鼠肾脏肝X受体表达及其活性的影响

目的探讨肝X受体(LXR)激动剂T0901317对db/db小鼠肾脏肝X受体表达水平及其活性的影响。方法将8周龄雄性db/db小鼠分为db/db组和db/db+T0901317组(均n=7),同时以同龄同性别野生型C57BL/6小鼠为对照组(n=7)。对照组和db/db组小鼠胃饲生理盐水(50μl/只/天×7),db/db+T0901317组小鼠胃饲T0901317[12.5 mg/(kg·d)×7];4周后RT-PCR检测肾组织ABCA1 mRNA水平;Western blot检测上述各组小鼠肾组织LXRα、LXRβ蛋白表达水平。结果与对照组相比,db/db组LXRα蛋白表达量、ABCA1 mRNA表达水平明显下调(P0.05);与db/db组相比,db/db+T0901317组上述指标表达上调(P0.05);与db/db组相比,T0901317组LXRβ蛋白表达差异无统计学意义(P0.05),而对照组LXRβ蛋白下调(P0.05)。结论 LXR可能通过激活LXRα进而上调ABCA1以减轻糖尿病引起的肾脏炎症性损害,为拮抗糖尿病所致的肾脏炎症性损伤提供新的理论依据。     

生长分化因子11对db/db糖尿病小鼠胰岛β细胞功能的保护作用及机制研究

目的探讨生长分化因子11(GDF11)对瘦素受体基因纯合突变(db/db)糖尿病小鼠胰岛β细胞的保护作用及影响机制。方法将20只8周龄的C57B/6J野生型小鼠制备为db/db糖尿病模型,并随机分为GDF11组和DM组,每组各10只;GDF11组小鼠给予GDF11重组蛋白注射,DM组小鼠给予磷酸盐缓冲液(PBS)注射,连续注射6周;并选取10只同龄正常小鼠作为对照组(NC组),给予6周PBS干预。观察GDF11对小鼠生理生化指标、胰岛β细胞功能以及胰岛Smad2、P-Smad2表达水平的影响。结果经GDF11干预后,db/db糖尿病小鼠的空腹血糖(FBS)、糖化血红蛋白(Hb A1C)、总胆固醇(TC)、三酰甘油(TG)、游离脂肪酸(FFA)均明显低于DM组及NC组小鼠(P<0.05);db/db糖尿病小鼠的糖耐量水平显著改善,GDF11组小鼠的血清胰岛素、血清胰升糖素均明显低于DM组(P<0.05),且均高于NC组(P<0.05);GDF11组小鼠的胰岛内胰岛素的水平明显高于DM组(P<0.05),但低于NC组(P<0.05);DM组与GDF11组小鼠的胰岛内胰升糖素无显著差异(P>0.05),且均高于NC组(P<0.05);经实时荧光定量PCR检测发现GDF11组小鼠胰岛胰十二指肠同源异型盒基因(Pdx-1)、亮氨酸拉链蛋白Maf家族A(MafA)、Nk同源异型盒基因家族6.1(Nkx6.1)、Insulin2基因表达上调;小鼠的p-Smad2、Smad2蛋白水平明显高于NC组小鼠(P<0.05)。结论GDF11可控制糖尿病小鼠胰升糖素分泌水平,调节β细胞转录因子表达,改善β细胞功能和含量,促进胰岛素的分泌合成,从而延缓糖尿病的发生和发展;GDF11对胰岛β细胞的保护作用可能与胰岛Smad2信号通路密切相关。     

平糖益肾汤联合厄贝沙坦片治疗早期糖尿病肾病的疗效分析

目的:探究平糖益肾汤联合厄贝沙坦片治疗早期糖尿病肾病的疗效及对糖脂代谢和肾功能的影响。方法:选取2016年3月~2017年5月我院收治的60例早期糖尿病肾病患者作为研究对象,随机分为对照组与治疗组,每组30例,对照组口服厄贝沙坦进行治疗,治疗组口服平糖益肾汤联合厄贝沙坦进行治疗,观察并记录两组患者的治疗总有效率、治疗前后的血糖水平及尿蛋白变化情况。结果:给药后,治疗组的总有效率为90.00%,明显高于对照组的50.00%,差异有统计学意义,P<0.05;治疗组的血糖浓度、Hb A1c浓度和尿蛋白浓度均低于对照组和本组治疗前的水平,差异均有统计学意义,P<0.05。结论:采用平糖益肾汤配合西药厄贝沙坦治疗早期糖尿病肾病,有利于提高患者的糖代谢,改善肾功能,延缓患者身体恶化的情况。     

阿托伐他汀联合厄贝沙坦治疗糖尿病肾病疗效观察

[目的]观察阿托伐他汀联合厄贝沙坦治疗糖尿病肾病的疗效.[方法]99例糖尿病肾病患者随机分成治疗组和对照组.两组患者均在严格执行糖尿病饮食、减少蛋白摄入、控制血糖、血压达标的基础上,治疗组给厄贝沙坦150 mg/d口服,同时给阿托伐他汀20 mg/d口服;对照组单用厄贝沙坦150 mg/d口服.两组均随访3个月.[结果]两组治疗后血肌酐(Scr)、尿白蛋白排泄率(UAER)均有改善(对照组P<0.05,治疗组P<0.01),治疗组效果优于对照组(P<0.05);治疗组治疗后,C-反应蛋白(CRP)及总胆固醇(TC)下降明显(P<0.05),而对照组治疗前后差畀无显著性(P>0.05).[结论]阿托伐他汀联合厄贝沙坦治疗糖尿病肾病能降低血胆固醇含量并发挥抗炎作用、减少尿蛋白排泄、改善肾功能、延缓肾功能衰竭的发生.     

硝苯地平联合厄贝沙坦治疗糖尿病合并高血压的疗效分析

探讨硝苯地平联合厄贝沙坦治疗糖尿病合并高血压的临床疗效。选取接受治疗的糖尿病合并高血压患者40例,随机将其分为治疗组和对照组各20例。对照组患者进行单纯的硝苯地平治疗,治疗组在硝苯地平治疗的基础上,联合厄贝沙坦治疗,比较两组患者糖尿病、高血压等指标的改善情况。经过1个疗程的治疗,两组患者的血压和血糖等指标均有下降。治疗组和对照组比较,显效率和总有效率较高,差异明显,有统计学意义（P〈0.05）。硝苯地平联合厄贝沙坦治疗糖尿病合并高血压的疗效较好,值得进行大规模临床推广。     

硝苯地平联合厄贝沙坦治疗糖尿病合并高血压的临床研究

研究硝苯地平联合厄贝沙坦对糖尿病合并高血压的治疗作用及安全性。选取2015年1月~2017年1月我院收治的168例糖尿病合并高血压患者。随机分为对照组和观察组各84例。给予对照组硝苯地平单药治疗,给予观察组硝苯地平+厄贝沙坦联合治疗,比较两组的疗效及安全性差异。结果与对照组比较,观察组的血压、血糖水平显著改善,血清炎性因子水平显著降低,差异有统计学意义(P0.05);两组的不良反应发生率比较未见统计学意义(P0.05)。硝苯地平与厄贝沙坦联合治疗糖尿病合并高血压安全、有效,对于维持血糖、血压平稳,提高患者生活质量有重要作用。     

硝苯地平联合厄贝沙坦治疗糖尿病合并高血压的疗效

目的：探讨对糖尿病合并高血压患者采用硝苯地平联合厄贝沙坦治疗的临床治疗效果。方法本次研究对象选取本院在2015年7月至2016年6月期间收治的66例糖尿病合并高血压患者,按照患者的入院顺序将其随机分成两组,治疗组和对照组患者各33例。对照组患者采取厄贝沙坦进行治疗,治疗组患者在厄贝沙坦治疗基础上联合硝苯地平进行治疗,比较两组患者临床治疗效果。结果治疗组患者总有效率为94．0％明显优于对照组的78．8％;治疗后,治疗组患者舒张压与收缩压明显低于对照组,差异具有统计学意义（P＜0．05）。结论硝苯地平联合厄贝沙坦治疗糖尿病合并高血压患者具有确切的临床治疗效果,能够有效地平稳降压,控制血糖。     

彩色多普勒超声评估厄贝沙坦对糖尿病肾病大鼠肾脏血流动力的影响

目的运用彩色多普勒超声评估厄贝沙坦对糖尿病肾病大鼠肾脏血流动力的影响。方法雄性SD大鼠随机分为3组:对照组、糖尿病肾病组(DN组)、厄贝沙坦组。给予相应的干预8周后,测量收缩期峰值流速(Vsmax)、舒张期最低流速(Vdmin)及阻力指数(RI),检测血尿指标,比较各组之间的差异,并做相关分析。结果彩色多普勒动态观察,DN组大鼠肾脏主肾动脉、段动脉血流信号清晰可见,部分叶间或弓形动脉粗细不等或血流信号减少,彩色多普勒血流呈非典型树支状分布。厄贝沙坦组肾脏血流信号改善,接近对照组。DN组和厄贝沙坦组Vsmax和Vdmin较对照组显著降低,进一步的组间比较显示厄贝沙坦组Vsmax和Vdmin显著高于DN组,分别为21.52±4.31cm/s vs 16.63±2.85cm/s,P=0.005和8.07±1.66cm/s vs 5.41±1.11cm/s,P=0.002,而RI低于DN组(0.62±0.12vs 0.73±0.14,P=0.046)。DN组和厄贝沙坦组体重、肾重、相对肾质量、血糖和24h尿蛋白量显著高于对照组(P0.001);与DN组比较,厄贝沙坦组肾重、相对肾质量和24h尿蛋白量显著下降(P0.05)。进一步的相关分析显示24h-UP与Vsmax和Vdmin呈负相关,相关系数分别为-0.869和-0.846(P0.001),而与RI呈正相关(r=0.767,P0.001)。结论彩色多普勒超声检查显示厄贝沙坦可改善糖尿病肾病大鼠肾脏血流动力。     

益气滋阴活血化瘀法联合厄贝沙坦治疗糖尿病肾病的疗效

目的:研究益气滋阴活血化瘀法联合厄贝沙坦治疗糖尿病肾病的疗效。方法:选取2015年1月～2016年7月收治的80例糖尿病肾病患者作为研究对象,采用电脑随机法分为对照组和观察组,各40例。观察组采用益气滋阴活血化瘀法联合厄贝沙坦治疗;对照组仅用厄贝沙坦治疗,比较两组治疗效果、中医证候积分和各项临床指标。结果:观察组总有效率高于对照组,差异有统计学意义(P0.05);治疗后,观察组的各项中医证候积分均低于对照组,差异均有统计学意义(P0.05);观察组血糖、肌酐、尿白蛋白排泄率指标均低于对照组,差异均有统计学意义(P0.05)。结论:益气滋阴活血化瘀法联合厄贝沙坦治疗糖尿病肾病的疗效显著,能降低患者的中医证候积分,并改善其各项临床指标。     

The dual peroxisome proliferator-activated receptor alpha/gamma activator muraglitazar prevents the natural progression of diabetes in db/db mice

There are two major defects in type 2 diabetes: 1) insulin resistance and 2) insulin deficiency due to loss of beta-cell function. Here we demonstrated that treatment with muraglitazar (a dual peroxisome proliferator-activated receptor alpha/gamma activator), when initiated before or after the onset of diabetes in mice, is effective against both defects. In study 1, prediabetic db/db mice were treated for 12 weeks. The control mice developed diabetes, as evidenced by hyperglycemia, hyperinsulinemia, reduced insulin levels in the pancreas, blunted insulin response to glucose, and impaired glucose tolerance. The muraglitazar-treated mice had normal plasma glucose, and insulin levels, equivalent or higher pancreatic insulin content than normal mice, showed a robust insulin response to glucose and exhibited greater glucose tolerance. In study 2, diabetic db/db mice were treated for 4 weeks. The control mice displayed increased glucose levels, severe loss of islets, and their isolated islets secreted reduced amounts of insulin in response to glucose and exendin-4 compared with baseline. In muraglitazar-treated mice, glucose levels were reduced to normal. These mice showed reduced loss of islets, and their isolated islets secreted insulin at levels comparable to baseline. Thus, muraglitazar treatment decreased both insulin resistance and preserved beta-cell function. As a result, muraglitazar treatment, when initiated before the onset of diabetes, prevented development of diabetes and, when initiated after the onset of diabetes, prevented worsening of diabetes in db/db mice.     

Glucagon-like peptide 1 receptor agonist ZP10A increases insulin mRNA expression and prevents diabetic progression in db/db mice

We characterized the novel, rationally designed peptide glucagon-like peptide 1 (GLP-1) receptor agonist H-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSK KKKKK-NH2 (ZP10A). Receptor binding studies demonstrated that the affinity of ZP10A for the human GLP-1 receptor was 4-fold greater than the affinity of GLP-1 (7-36) amide. ZP10A demonstrated dose-dependent improvement of glucose tolerance with an ED50 value of 0.02 nmol/kg i.p. in an oral glucose tolerance test (OGTT) in diabetic db/db mice. After 42 days of treatment, ZP10A dose-dependently (0, 1, 10, or 100 nmol/kg b.i.d.; n = 10/group), decreased glycosylated hemoglobin (HbA1C) from 8.4 +/- 0.4% (vehicle) to a minimum of 6.2 +/- 0.3% (100 nmol/kg b.i.d.; p < 0.05 versus vehicle) in db/db mice. Fasting blood glucose (FBG), glucose tolerance after an OGTT, and HbA1C levels were significantly improved in mice treated with ZP10A for 90 days compared with vehicle-treated controls. Interestingly, these effects were preserved 40 days after drug cessation in db/db mice treated with ZP10A only during the first 50 days of the study. Real-time polymerase chain reaction measurements demonstrated that the antidiabetic effect of early therapy with ZP10A was associated with an increased pancreatic insulin mRNA expression relative to vehicle-treated mice. In conclusion, long-term treatment of diabetic db/db mice with ZP10A resulted in a dose-dependent improvement of FBG, glucose tolerance, and blood glucose control. Our data suggest that ZP10A preserves beta-cell function. ZP10A is considered one of the most promising new drug candidates for preventive and therapeutic intervention in type 2 diabetes.     

Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes

We have generated mice that carry a neuron-specific leptin receptor (LEPR) transgene whose expression is driven by the rat synapsin I promoter synapsin-LEPR B (SYN-LEPR-B). We have also generated mice that are compound hemizygotes for the transgenes SYN-LEPR-B and neuron-specific enolase-LEPR B (NSE-LEPR-B). We observed a degree of correction in db/db mice that are hemizygous (Syn db/db) and homozygous (Syn/Syn db/db) for the SYN-LEPR-B transgene similar to that previously reported for the NSE-LEPR-B transgene. We also show complete correction of the obesity and related phenotypes of db/db mice that are hemizygous for both NSE-LEPR-B and SYN-LEPR-B transgenes (Nse+Syn db/db). Body composition, insulin sensitivity, and cold tolerance were completely normalized in Nse+Syn db/db mice at 12 weeks of age compared with lean controls. In situ hybridization for LEPR B isoform expression in Nse+Syn db/db mice showed robust expression in the energy homeostasis-relevant regions of the hypothalamus. Expression of 3 neuropeptide genes, agouti-related peptide (Agrp), neuropeptide Y (Npy), and proopiomelanocortin (Pomc), was fully normalized in dual transgenic db/db mice. The 2 transgenes in concert conferred normal fertility to male and female db/db mice. Male mice with partial peripheral deletion of Lepr, induced in the periweaning phase, did not show alterations in body composition or mass. In summary, we show that brain-specific leptin signaling is sufficient to reverse the obesity, diabetes, and infertility of db/db mice.     

香烟烟雾暴露对小鼠糖代谢的影响及穿心莲内酯的干预效果

目的探讨香烟烟雾暴露对小鼠糖代谢的影响及穿心莲内酯的干预效果,为糖尿病预防及烟草控制提供依据。方法选择SPF级C57BL/6J品系雄性小鼠60只,按照小鼠体重随机分为正常对照组(A组)、烟雾暴露组(B组)和烟雾暴露+穿心莲内酯干预组(C组),每组20只。B组和C组小鼠每天暴露于20支香烟的烟雾60 min,持续3个月;C组小鼠每周腹腔内注射穿心莲内酯(10 mg/kg),A组和B组注射同等体积生理盐水。香烟烟雾暴露结束后施行腹腔内注射葡萄糖耐量实验(IPGTT)和胰岛素耐量实验(IPITT),比较各组小鼠各时点血糖变化及IPGTT和IPITT血糖水平的曲线下面积。结果 0 min时,B组的血糖最高,C组次之。IPGTT示,腹腔注射葡萄糖后各组小鼠的血糖水平迅速增加,注射后15 min最高,随后逐渐下降,且B组在15 min和30 min时的血糖水平均显著高于A组(P<0.01);B组和C组血糖水平的曲线下面积均显著大于A组(P<0.05),B组显著大于C组(P<0.05)。IPITT示,腹腔注射胰岛素后,15 min时B组血糖水平显著高于A组(P<0.05),3...     

Lactobacillus rhamnosus GG improves glucose tolerance through alleviating ER stress and suppressing macrophage activation in db/db mice

Although recent studies have reported that Lactobacillus rhamnosus GG (LGG), the most extensively studied probiotic strain, exerts an anti-hyperglycemic effect on several rodent models, the underlying mechanism remains unclear. In this study, twenty male C57BL/KsJ-db/db (db/db) mice were divided into 2 groups, LGG-treated and control group, which received a daily dose of LGG (1 × 10⁸ CFU per mouse) and PBS orally for 4 weeks, respectively. We observed that glucose tolerance was significantly improved in LGG-treated db/db mice. Insulin-stimulated Akt phosphorylation and GLUT4 translocation were higher in skeletal muscle of LGG-treated mice relative to their controls. It was also observed that LGG treatment caused significant reductions in endoplasmic reticulum (ER) stress in skeletal muscle and M1-like macrophage activation in white adipose tissues. Our results indicate that the anti-diabetic effect of LGG in db/db mice is associated with alleviated ER stress and suppressed macrophage activation, resulting in enhanced insulin sensitivity. These findings suggest a therapeutic potential of probiotics for prevention and treatment of type 2 diabetes.     

Glycemic improvement in diabetic db/db mice by overexpression of the human insulin-regulatable glucose transporter (GLUT4).

The effects of increased GLUT4 (insulin-regulatable muscle/fat glucose transporter) expression on glucose homeostasis in a genetic model of non-insulin-dependent diabetes mellitus were determined by expressing a human GLUT4 transgene (hGLUT4) in diabetic C57BL/KsJ-db/db mice. A genomic hGLUT4 construct was microinjected directly into pronuclear murine embryos of db/+ matings to maintain the inbred background. Four lines of hGLUT4 transgenic mice were bred to homozygosity at the db locus and all showed a marked reduction of both fasted and fed plasma glucose levels (to approximately 50 and 360 mg/dl, respectively) compared with age-matched nontransgenic db/db mice (approximately 215 and 550 mg/dl, respectively), as well as an enhanced disposal of an oral glucose challenge. In situ immunocytochemical localization of GLUT4 protein in muscle from hGLUT4 db/db mice showed elevated plasma membrane-associated GLUT4 protein in the basal state, which markedly increased after an insulin/glucose injection. In contrast, nontransgenic db/db mice had low levels of plasma membrane-associated GLUT4 protein in the basal state with a relatively small increase after an insulin/glucose challenge. Since the intracellular GLUT4 levels in db/db mice were similar to nontransgenic db/+ mice, the glucose transport defect in db/db mice is at the level of glucose transporter translocation. Together, these data demonstrate that GLUT4 upregulation overcomes the glucose transporter translocation defect and alleviates insulin resistance in genetically diabetic mice, thus resulting in markedly improved glycemic control.     

Gene therapy of diabetes using a novel GLP-1/IgG1-Fc fusion construct normalizes glucose levels in db/db mice

Glucagon-like peptide (GLP-1), a major physiological incretin, plays numerous important roles in modulating blood glucose homeostasis and has been proposed for the treatment of type 2 diabetes. The major obstacles for using native GLP-1 as a therapeutic agent are that it must be delivered by a parenteral route and has a short half-life. In an attempt to develop a strategy to prolong the physiological t(1/2) and enhance the potency of GLP-1, a fusion protein consisting of active human GLP-1 and mouse IgG(1) heavy chain constant regions (GLP-1/Fc) was generated. A plasmid encoding an IgK leader peptide-driven secretable fusion protein of the active GLP-1 and IgG(1)-Fc was constructed for mammalian expression. This plasmid allows for expression of bivalent GLP-1 peptide ligands as a result of IgG-Fc homodimerization. In vitro studies employing purified GLP-1/Fc indicate that the fusion protein is functional and elevates cAMP levels in insulin-secreting INS-1 cells. In addition, it stimulates insulin secretion in a glucose concentration-dependent manner. Intramuscular gene transfer of the plasmid in db/db mice demonstrated that expression of the GLP-1/Fc peptide normalizes glucose tolerance by enhancing insulin secretion and suppressing glucagon release. This strategy of using a bivalent GLP-1/Fc fusion protein as a therapeutic agent is a novel approach for the treatment of diabetes.     

Hypoglycemic effect of aqueous shallot and garlic extracts in rats with fructose-induced insulin resistance

The present study has been carried out to investigate the effect of aqueous extract of shallot (Allium ascalonicum) and garlic (Allium satium) on the fasting insulin resistance index (FIRI) and intraperitoneal glucose tolerance test (IPGTT) of fructose-induced insulin resistance rats. Male albino Wistar rats were fed either normal or high-fructose diet for a period of eight weeks. Fasting blood glucose level, fasting blood triglyceride level, FIRI, and the area under the glucose tolerance curve were significantly elevated in fructose-fed animals. Fructose-induced insulin resistance rats treated by aqueous shallot or garlic extract (500 mg/kg body weight/day, i.p.) for duration of eight weeks. Control animals only received normal saline (0.9%). The results showed that neither shallot nor garlic extracts significantly altered the FIRI and the IPGTT at the fourth week after treatment. The fasting blood glucose in fructose-induced insulin resistance animals has been significantly decreased in 8-week treated animals by both shallot and garlic extracts. Shallot extract administration, but not garlic extract, for a period of eight weeks can significantly improve the intraperitoneal glucose tolerance and diminish the FIRI. These results indicate that shallot and garlic extracts have a hypoglycemic influence on the fructose-induced insulin resistance animals and aqueous shallot extract is a stronger hypoglycemic agent than the garlic extract.     

小檗碱影响AMPK/PGC-1信号途径改善糖尿病胰岛素抵抗和线粒体功能的研究

目的探讨小檗碱改善糖尿病鼠糖代谢及胰岛素抵抗作用及对骨骼肌线粒体功能的影响和机制。方法采用db/db小鼠为研究对象,以野生型小鼠为对照组。给予小檗碱(5 mg·kg-1·d-1)腹腔注射3周,观察食量、体重和空腹血糖水平;第3周末处死,留取血标本分离血清,检测胰岛素水平并计算胰岛敏感指数,留取附睾脂肪垫并称重;提取腓肠肌线粒体,检测细胞色素C氧化酶活性和ATP定量,Western blot检测腓肠肌AMPK/PGC-1α表达。结果小檗碱给药3周后,db/db小鼠的体重和脂肪垫重量均显著降低,血糖水平下降,胰岛素敏感指数改善;但给药前后的胰岛素释放水平无明显改变。小檗碱可一定程度地升高骨骼肌线粒体COX活性水平,明显提高ATP含量,并使AMPK磷酸化水平显著激活,PGC-1α转录活性增强。结论小檗碱具有明显的降糖、降脂、改善胰岛素抵抗作用,其降糖作用与刺激胰岛素释放水平无关,而与激活AMPK/PGC-1α信号途径,提高线粒体能量代谢有关。