中国劲酒对肾阳虚模型大鼠下丘脑-垂体-肾上腺轴及免疫功能的影响

目的:研究中国劲酒对皮质酮致肾阳虚模型的大鼠下丘脑-垂体-肾上腺(Hypothalamic-pituitary adrenal,HPA)轴及免疫功能的影响。方法:取健康清洁级雄性SD大鼠45只,按随机数字表法分为空白对照组、模型组和中国劲酒组,每组15只,通过皮下注射外源性皮质酮(10 mg/kg体重)连续14天抑制HPA轴,制备肾阳虚模型。皮质酮注射前5天,以50 ml/kg体重灌胃中国劲酒(相当于中国劲酒日推荐服用剂量的30倍),连续19天。采用酶联免疫吸附试验(ELISA)方法检测血浆皮质酮(Corticosterone,CORT)含量;采用放射性免疫法测定血浆中促肾上腺皮质激素(Adrenocorticotropic hormore,ACTH)含量,采用实时定量-聚合酶链反应法(Real-time PCR)测定下丘脑促肾上腺皮质激素释放激素(Corticotropin releasing hormone,CRH)mRNA表达水平;取胸腺称重,淋巴细胞凋亡及增殖率分别采用流式细胞仪法和改良四氮唑盐(XTT)法。结果:在外源性皮质酮作用下,肾阳虚模型大鼠较空白对照组HPA轴和免疫功能受到明显抑制,中国劲酒灌胃后可显著提高大鼠下丘脑CRH mRNA水平、血浆ACTH含量,与肾阳虚模型组比较差异有统计学意义(P<0.05);血浆CORT水平有升高倾向;同时在免疫调节方面,中国劲酒可明显增加皮质酮模型大鼠胸腺重量和降低脾脏淋巴细胞凋亡率,与肾阳虚模型组比较差异有统计学意义(P<0.01);中国劲酒有促进淋巴细胞增殖的趋势。结论:中国劲酒能改善肾阳虚模型大鼠HPA轴功能;也具有改善肾阳虚模型大鼠免疫功能的作用。     

褪黑素水平对抑郁症患者下丘脑-垂体-肾上腺轴功能的影响

目的探讨抑郁症患者褪黑素(MT)水平对下丘脑-垂体-肾上腺轴(HPA)功能的影响。方法对86例抑郁症患者,检测血清MT、促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质醇(COR),并分析其相互关系。结果1以MT中位数(51.3ng/L)为切点,将所有抑郁症患者分为MT高值组(51.3ng/L,n=43)与MT低值组(51.3ng/L,n=43),前者血清CRH、ACTH、COR均显著低于后者(t=3.330,3.315,2.314;P0.01,0.01,0.05);2血清MT水平与CRH、ACTH水平负相关(r=-0.414,-0.329;P0.01,0.05)。结论褪黑素对抑郁症患者的HPA轴功能可能有一定的抑制作用。     

下丘脑-垂体-肾上腺轴在抑郁症发病中的作用

越来越多的研究表明，下丘脑一垂体一肾上腺轴(hypothalamic pituitary adrenal axic，HPA轴)在抑郁的发病机制中发挥着重要的作用。HPA轴的活化机制是：下丘脑通过垂体门脉系统运送下丘脑调节肽(促肾上腺皮质激素释放激素，CRH)到脑垂体，从而调节腺垂体的分泌。腺垂体在调节肽的作用下释放促肾上腺皮质激素(ACTH)，然后作用于肾上腺皮质，释放肾上腺皮质激素到全身。下面我们将从HPA轴的三个水平(CRH、ACTH、肾上腺皮质激素)来论述HPA轴在抑郁发病过程中的作用。     

褪黑素对创伤后应激障碍大鼠下丘脑-垂体-肾上腺轴的影响

目的:探讨褪黑素(MLT)对足部电击所致创伤后应激障碍(PTSD)大鼠下丘脑-垂体-肾上腺(HPA)轴的影响。方法:利用足底电击法制备大鼠PTSD模型,通过腹腔注射方法给予治疗组大鼠MLT。通过拒俘反应测试检测大鼠的行为学变化,利用real time RT-PCR方法检测下丘脑中促肾上腺皮质激素释放激素(CRH)mRNA的表达,利用酶联免疫吸附试验(ELISA)检测血清中促肾上腺皮质激素(ACTH)、肾上腺素(EPI)和糖皮质激素(GC)的含量。结果:PTSD组大鼠拒俘反应明显(P<0.05),下丘脑中CRH mRNA表达升高(P<0.05),血清中ACTH和EPI明显升高(P<0.05),但是GC水平下降(P<0.05)。MLT治疗后可以明显缓解PTSD大鼠拒俘反应(P<0.05),同时降低下丘脑中CRH mRNA表达(P<0.05),降低血清中ACTH和EPI水平并升高GC的水平(P<0.05)。结论:MLT治疗可缓解PTSD大鼠的症状,并恢复HPA轴的神经内分泌平衡。     

强肌健力饮对肾阳虚大鼠CRH、ACTH、Cor水平的影响

目的:观察强肌健力饮对肾阳虚大鼠下丘脑组织中促肾上腺皮质激素释放激素(CRH)及血浆促肾上腺皮质激素(ACTH)、皮质醇(Cor)水平的影响,进一步探讨该方对中医肾阳虚证的防治机理.方法:将大鼠分为正常对照组、肾阳虚模型组、强肌健力饮低、中、高剂量组、右归丸阳性对照组,采用氢化可的松制备肾阳虚大鼠模型.观察动物的一般状态及其胸腺和肾上腺指数,采用放射免疫分析检测CRH、ACTH、Cor的含量.结果:①肾阳虚模型组大鼠体重及胸腺指数、肾上腺指数明显低于正常对照组(P＜0.01),CRH、ACTH、Cor含量均比正常对照组显著降低(P＜0.01).②强肌健力饮各剂量组CRH、ACTH、Cor含量均比肾阳虚模型组显著升高(P＜0.05～0.01).结论:肾阳虚时下丘脑-垂体-肾上腺轴合成、分泌和调控功能低下,而强肌健力饮能够修复该轴功能的损伤,表明该方药具有下丘脑、垂体、肾上腺轴多层次的调节作用.     

外源性糖皮质激素对大鼠下丘脑─垂体─肾上腺─胸腺轴的影响

本文观察大鼠每天皮下注射皮质酮（1~50mg/kg，连续14天）后下丘脑─垂体─肾上腺─胸腺（HPAT）轴的形态与机能改变。结果表明：实验大鼠垂体，肾上腺，胸腺重量减轻，下丘脑单胺类递质含量升高，下丘脑室旁核促肾上腺皮质素释放因子（CRF）分泌细胞及正中隆起CRY神经纤维和垂体前叶促肾上腺皮质激素（ACTH）分泌细胞等数量减少，染色变淡，血浆皮质酮（CORT）和ACTh浓度降低。淋巴细胞增殖反应及自然杀伤细胞活性减弱，T淋巴细胞产生IL-2、IFN－γ能力下降。提示：（1）外源性糖皮质激素剂量依赖性反馈抑制HPAT轴；（2）与此同时激活下丘脑单胺类递质，进一步支持糖皮质激素与儿茶酚胺共同构成HPAT重要调节因素的观点。     

慢性应激抑郁模型大鼠下丘脑-垂体-肾上腺轴负反馈功能与蒙药槟榔十三味丸的干预

背景:抑郁症是具有很高的致死、致残率,严重威胁着人类健康的常见精神疾患。临床上应用槟榔十三味丸治疗抑郁症取得良好的疗效。但其作用机制尚未明确。目的:观察蒙药槟榔十三味丸对慢性应激抑郁模型大鼠下丘脑-垂体-肾上腺轴负反馈功能的影响,探讨槟榔十三味丸抗抑郁作用机制。方法:80只Wistar雄性大鼠,根据蔗糖水消耗量随机分为正常对照组、模型组、氟西汀组、槟榔十三味丸低、中、高剂量组、RU486组和槟榔十三味丸低、中、高剂量+RU486组,每组8只。除正常对照组外,其余大鼠均采用慢性应激结合孤养方法制备抑郁模型,槟榔十三味丸低、中、高剂量组大鼠在造模同时连续28 d灌胃槟榔十三味丸0.2,0.4,0.8 g/kg;正常对照组和模型组大鼠灌胃羧甲基纤维素钠;RU486组大鼠自造模第21天起腹部皮下注射糖皮质激素受体拮抗剂RU486;槟榔十三味丸低、中、高剂量+RU486组大鼠在造模同时灌胃槟榔十三味丸0.2,0.4,0.8 g/kg,且自造模第21天起腹部皮下注射RU486。结果与结论:与正常对照组相比,模型组及RU486组大鼠肾上腺皮质酮水平显著升高(P0.05),海马、下丘脑、垂体糖皮质激素受体m RNA表达显著下降,下丘脑促肾上腺皮质激素释放激素m RNA表达显著增多;与模型组相比,灌胃槟榔十三味丸的大鼠肾上腺皮质酮水平降低,海马、下丘脑、垂体糖皮质激素受体m RNA表达明显增多,下丘脑促肾上腺皮质激素释放激素m RNA表达水平显著降低;且与RU486组相比,同时灌胃槟榔十三味丸的大鼠肾上腺皮质酮、海马、下丘脑、垂体糖皮质激素受体m RNA、下丘脑促肾上腺皮质激素释放激素m RNA表达水平也出现改变。提示槟榔十三味丸对糖皮质激素的过度分泌有直接的调控作用,并可通过增强糖皮质激素受体m RNA的表达及降低促肾上腺皮质激素释放激素m RNA的表达,改善下丘脑-垂体-肾上腺轴负反馈中枢的功能障碍。当下丘脑-垂体-肾上腺轴负反馈通路被阻断后,槟榔十三味丸作用减弱。     

外源性ADM对肾脏急性机械性损伤早期HPA轴的影响

目的: 研究外源性肾上腺髓质素(ADM)的运用对肾脏急性机械性损伤早期下丘脑-垂体-肾上腺皮质(HPA)轴的影响,探讨外源性ADM在急性创伤中的生物学作用。方法: 健康成年普通级Wistar大鼠104只,随机分为4组:正常对照组(8只)、单纯创伤组(32只)、伤前给药组(32只)、伤后给药组(32只);后3组采用自由落体打击仪直接打击大鼠脊肋区制作肾脏机械性损伤模型。2个给药组分别于损伤前后10 min腹腔注射ADM(0.1 nmol/kg)。3 组肾损伤大鼠分为4 批分别于创伤后1、6、12、24 h采用快速心脏采血法处死。迅速解剖动物提取下丘脑标本,采用免疫组化染色法检测促肾上腺皮质激素释放激素(CRH)在下丘脑的表达;放免分析法检测血浆促肾上腺皮质激素(ACTH)、皮质醇(CORT)浓度。结果: 单纯创伤组下丘脑CRH的表达及血浆ACTH、CORT浓度较正常对照组轻微升高,但无显著差异;创伤前注射ADM使创伤后下丘脑CRH的表达在1、24 h,血浆ACTH浓度在12 h,以及血浆CORT浓度在6、12、24 h显著高于单纯创伤组及正常对照组(P<0.05);创伤后注射ADM使下丘脑CRH的表达在1、6、12 h,以及血浆CORT浓度在12、24 h明显高于单纯创伤组及正常对照组(P<0.05)。结论: 外源性ADM可激活HPA轴,使HPA轴各个层面的活动增强,但不同层面对外源性ADM的反应性不同,创伤前、后注射ADM对HPA轴的影响不同。     

褪黑素对大鼠下丘脑-垂体-肾上腺轴及免疫功能受抑状态的影响

目的 :探讨外源性褪黑素对下丘脑 垂体 肾上腺轴及免疫功能受抑状态的影响。方法 :采用放射免疫法及细胞免疫技术分别观察了两个不同剂量 (10 0、2 0 0 μg kg)褪黑素连续 14天腹腔注射 ,对皮质酮诱导的HPA轴及免疫功能受抑大鼠血浆ACTH ,皮质酮水平以及淋巴细胞增殖 ,NKCC杀伤活性和ConA诱生的IL 2水平的影响。结果 :褪黑素 10 0 μg kg处理动物 ,其明显下降的血浆ACTH及皮质酮水平均有上升趋势 ,但在统计学上无显著意义 ,而褪黑素 2 0 0 μg kg处理动物 ,其血浆ACTH及皮质酮水平的上升与皮质酮对照组相比有显著意义 (P <0 0 5 )。对免疫功能的影响 ,无论褪黑素 10 0 μg kg还是 2 0 0μg kg处理动物 ,其被抑制的细胞免疫功能 (淋巴细胞增殖、NKCC及IL 2水平 )均有所恢复 ,且与皮质酮对照组相比 ,差异显著(P <0 0 5 )。结论 :外源性褪黑素可改善皮质酮诱导的大鼠HPA轴及免疫功能受抑状态。     

赛庚啶对大鼠垂体-肾上腺皮质轴的作用观察

目的　研究赛庚啶 (cyproheptadine ,CYP)对大鼠垂体、肾上腺皮质超微结构的影响。 方法　用透射电子显微镜观察经 4 6mg/kg/d赛庚啶灌胃后垂体、肾上腺皮质超微结构的改变。结果　实验组大鼠肾上腺皮质束状带细胞线粒体结构不清 ,异染色质边集 ,核周隙明显增宽 ,细胞核固缩 ,出现退行性改变。垂体促肾上腺皮质激素细胞线粒体嵴肿胀、断裂 ,出现髓样变 ,粗面内质网脱颗粒 ,胞浆内分泌颗粒明显减少。结论　赛庚啶对大鼠垂体、肾上腺皮质超微结构产生明显影响     

Histological and morphofunctional parameters of the hypothalamic–pituitary–adrenal system are sensitive to daidzein treatment in the adult rat

The isoflavone, daidzein is a biologically active, plant-derived compound that interacts with estrogen receptors. Data from previous studies have suggested that daidzein exerts beneficial effects in many diseases; however, as an endocrine disrupter, it may also alter the functioning of the endocrine system. Data regarding the effect of daidzein on the morphofunctional and histological parameters of the hypothalamic–pituitary–adrenal (HPA) system is still lacking. Therefore, using the newCAST stereological software, we investigated the effects of chronic (21 days) daidzein treatment on corticotropin-releasing hormone (CRH) neurons within the hypothalamus and corticotropes (ACTH cells) in the pituitary, while image analysis was employed to-examine the intensity of fluorescence of CRH in the median eminence (ME) and adrenocorticotropin hormone in the pituitary in adult orchidectomized (Ovx) rats. Circulating ACTH and corticosterone levels were also analyzed. This study showed that daidzein treatment decreased the volume density of CRH neurons within the paraventricular nucleus as well as CRH immunofluorescence in the ME. The total number of ACTH cells was decreased, while ACTH cell volume and the intensity of ACTH fluorescence were increased following daidzein treatment. Both ACTH and corticosterone blood levels were increased after daidzein administration. The results of performed experiments clearly demonstrate that volume density of CRH neurons; total number and volume of ACTH cells, as well as stress hormones levels are vulnerable to the effects of daidzein.     

Hypothalamo-pituitary-adrenocortical dysregulation in aging F344/Brown-Norway F1 hybrid rats

Hypothalamo-pituitary-adrenocortical (HPA) axis aging was studied in young (3 mo), middle aged (15 mo) and aged (30 mo) F344/Brown Norway hybrid rats. This strain was selected to obviate HPA-relevant pathologies found in other aging models. Aged, unstressed rats showed enhanced central HPA drive, marked by elevated ACTH release and decreased pituitary proopiomelanocortin and corticotropin-releasing factor receptor 1 (CRH-R1) mRNAs. Acute corticosterone responses to spatial novelty were exacerbated in aged rats; however, responses to restraint or hypoxia were not affected. Chronic stress exposure also differentially increased HPA drive in aged animals, marked by elevated paraventricular nucleus CRH peptide levels and pituitary proopiomelanocortin mRNA. Plasma ACTH and pituitary POMC and CRH-R1 mRNA expression in middle-aged rats were intermediate those of young and aged animals. Middle-aged animals responded to chronic stress with disproportionate increases in CRH mRNA levels, and increased corticosterone secretion following hypoxia but not novelty. The results suggest a gradual increase in HPA tone across the aging process, culminating in marked hyperresponsivity to both acute and chronic stress in senescence.     

Effects of prolonged leptin infusion on rat pituitary-adrenocortical function.

Compelling evidence suggests that a regulatory loop between leptin and the hypothalamo-pituitary-adrenal (HPA) axis is operative, where ACTH inhibits leptin secretion by adipose tissue and in turn leptin increases expression and secretion of ACTH. However, conflicting findings have been obtained in vivo on the acute and chronic effects of leptin on the HPA axis. Adult female Wistar rats, kept in metabolic cages, were intraperitoneally infused for 2, 4, 8 or 16 days with leptin (10 nmol/kg. 24 h); control animals were infused with the vehicle only. The rate of body-weight gain was similar in control and leptin-infused rats. At day 16 of treatment relative pituitary weight was higher and relative adrenal weight smaller in leptin-infused than control rats. Pituitary ACTH concentration gradually decreased with the duration of treatment, and the drop was significantly higher in leptin-infused than control rats. During the entire experimental period the blood level of aldosterone was similar in both groups of rats. Conversely, at days 2 and 4 of treatment the blood concentration of corticosterone was lower in leptin-infused than in control rats, which at these times displayed elevated levels of circulating corticosterone. Taken together, these findings allow us to conclude that in the rat the prolonged infusion of low doses of leptin i) primarily depresses pituitary ACTH production, the effect being probably mediated by the hypothalamus; and ii) inhibits corticosterone response to the stress evoked by placing of animals in the metabolic cages.     

Restraint-induced corticosterone secretion and hypothalamic CRH mRNA expression are augmented during acute withdrawal from chronic cocaine administration

Stress responses during cocaine withdrawal likely contribute to drug relapse and may be intensified as a consequence of prior cocaine use. The present study examined changes in stressor-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis during acute withdrawal from chronic cocaine administration. Adult male Sprague-Dawley rats received daily administration of cocaine (30 mg/kg, i.p.) or saline for 14 days. Twenty-four hours after the last injection, rats in each group were sacrificed under stress-free conditions or following 30 min of immobilization. Plasma corticosterone (CORT) was measured in trunk-blood using radioimmunoassay, corticotropin-releasing hormone (CRH) mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus were measured using in situ hybridization and glucocorticoid receptor (GR) protein expression in the pituitary gland and dissected brain regions was measured using Western blot analysis. Basal CRH mRNA in the PVN was unaltered as a result of prior cocaine administration. However, a significant increase in CRH mRNA was observed 90 min following the termination of restraint in cocaine withdrawn, but not saline-treated, rats. Basal CORT was also unaffected by prior cocaine administration, but the CORT response measured immediately after restraint was significantly augmented in cocaine-withdrawn rats. Differences in GR protein expression in number of regions implicated in negative feedback regulation of HPA function, including the hypothalamus, were not observed. These findings indicate that the HPA response to stressors is intensified during early withdrawal from cocaine administration and may be independent of changes in GR-mediated negative feedback.     

硒对氧化偶氮甲烷所致大鼠结肠癌形成过程中垂体远侧部促肾上腺皮质激素阳性细胞的影响

目的观察硒对致癌剂氧化偶氮甲烷(AOM)所致大鼠结肠癌形成过程中,垂体远侧部ACTH阳性细胞的影响。方法随机将20只3周龄SPF级断乳雄性SD大鼠分为正常对照组、实验对照组、致癌剂前补硒组、致癌剂后补硒组。用AOM(15mg/kg)每周腹腔注射,连续2周,诱导大鼠结肠癌形成。亚硒酸钠(Na2SeO3)水溶液(4mg/L)分别在AOM前、后干预,并持续至实验结束。各组均于34周后取大鼠垂体,用免疫组织化学SP法,观察垂体远侧部ACTH阳性细胞的形态结构及免疫组织化学反应强度,并进行图像分析。结果亚甲基蓝染色光镜下观察,可见AOM腹腔注射的大鼠结肠黏膜出现异常隐窝(AC)和异常隐窝灶(ACF)。免疫组织化学法显示,实验对照组大鼠垂体远侧部ACTH阳性细胞与正常对照组比较,阳性反应显著性增强(P<0.01);硒干预的各组与实验对照组相比,ACTH阳性细胞的阳性反应进一步增强(P<0.01)。结论硒可增强AOM所致大鼠结肠癌形成过程中垂体远侧部ACTH阳性细胞的功能。     

Comparison of CRH test and ACTH test in patients with bronchial asthma]

Although glucocorticoid is the most effective agent for bronchial asthma, its systemic administration leads to suppression of adrenocortical function. Rapid ACTH test has been performed for assessing the function of the hypothalamic-pituitary-adrenocortical (HPA) system of asthmatics. Recently human corticotropin-releasing hormone (CRH) has been chemically synthesized. In order to evaluate clinical usefulness of CRH, we compared CRH test with ACTH test in 17 patients with bronchial asthma (3 patients out of them concurrently receiving prednisolone 5-10 mg/day). Both tests were carried out within 2 weeks after 6 month treatment with fluticasone propionate (800 micrograms/day) inhaled via pMDI. There is no significant difference between results obtained from the both tests. Thus, dividing subjects into high and low responders based on an extent of increases in plasma ACTH levels after the CRH injection, we found a significant difference in maximal plasma concentrations of cortisol between after CRH and ACTH injections in the low responders. Therefore, in some patients, CRH test provides more accurate assessment of the function of HPA system than ACTH test.     

Periodic maternal deprivation induces gender-dependent alterations in behavioral and neuroendocrine responses to emotional stress in adult rats.

There is evidence that stressful events during the neonatal "stress hyporesponsive period" may influence both emotional behavior and the maturation of the hypothalamic-pituitary-adrenal (HPA) axis in rats. We tested whether periodic maternal deprivation (180 min daily on postnatal days 3-10, PMD) caused chronic changes in emotional behavior and HPA axis activity in either male or female adult rats, or both. In addition, HPA secretory responses to human/rat corticotropin-releasing factor (CRH, 50 ng/kg i.v.) were determined in the adult males. In the elevated plus-maze test, adult (4-5 months of age) PMD-treated animals of both sexes displayed increased anxiety-related behavior compared to control rats. This was indicated by a reduction in the number of entries (male: 70% reduction, p < 0.01; female: 31% reduction, p < 0.01) and amount of time spent on the open arms (male: 86% reduction, p < 0.01; female: 40% reduction, NS). Neuroendocrine parameters were also altered in PMD-treated rats in a gender-dependent manner. Whereas basal plasma adrenocorticotropin (ACTH) and corticosterone levels did not differ significantly between PMD and control groups of either sex, the ACTH response to elevated plus-maze exposure, a predominantly emotional stressor, was higher in male (p < 0.01), but not female, PMD animals than in the respective controls. In contrast, PMD had no effect on behavioral (duration of struggling) or HPA axis responses to forced swimming (90 s, 19 degrees C), a complex and predominantly physical stressor, in either male or female rats. In response to CRH stimulation, PMD-treated males did not show differences in the ACTH secretion compared to controls, indicating alterations in HPA axis regulation at a suprapituitary level. Thus, PMD caused long-term changes in the emotional behavior of adult rats of both sexes, although to a differing degree in males and females, whereas it appeared to cause predominantly alterations in the HPA axis response in males, depending on the characteristics of the stressor used.     

Prolonged exendin-4 administration stimulates pituitary-adrenocortical axis of normal and streptozotocin-induced diabetic rats

Evidence is available that exendin-4 (EX4), a glucagon-like peptide-1 receptor (GLP-1R) agonist acutely stimulates hypothalamo-pituitary-adrenal (HPA) axis in the rat. EX4 is a potent insulinotropic agent, which is currently under clinical trial for treatment of type 2 diabetes. Since diabetes is known to affect adrenal function, we investigated the effects of the prolonged administration of EX4 and/or the GLP-1R antagonist EX4(9-39) (EX4-A) (daily subcutaneous injections of 1 nmol/kg EX4 and/or EX4-A, for 7 days) on the HPA axis of normoglycemic and streptozotocin (STZ)-induced diabetic rats. In STZ-untreated rats, chronic EX4 treatment did not change the blood level of ACTH. In contrast, it evoked a marked rise in the plasma concentrations of aldosterone and corticosterone, these effects being reversed by EX4-A. In STZ-induced diabetic rats, prolonged EX4 administration increased the plasma levels of ACTH, aldosterone and corticosterone. EX4-A did not prevent the first two effects of EX4, and annulled the latter one. These findings allow us to draw the following conclusions: i) EX4 prolonged exposure desensitizes hypothalamo-hypophyseal GLP-1R in normal rats, and exerts an ACTH-independent GLP-1R-mediated aldosterone and corticosterone secretagogue effect; and ii) experimental diabetes induces the expression of EX4 receptors other than the classic GLP-1R, whose activation mediate the ACTH and aldosterone, but not corticosterone, secretagogue effects. Our study provides evidence that metabolic dysregulations occurring in STZ-induced diabetic rats are able to profoundly affect the response of the HPA axis to GLP-1.     

番石榴叶总三萜对2型糖尿病大鼠的降血糖和血脂作用

目的: 探讨番石榴叶总三萜(TTPGL)对2型糖尿病大鼠血糖及血脂的影响。方法: 采用高糖高脂饮食加腹腔注射小剂量链脲佐菌素(STZ, 35 mg·kg^-1)方法建立2型糖尿病大鼠模型。将造模成功的糖尿病大鼠随机分为5组:糖尿病模型组,TTPGL低、中、高剂量组(60、120、240 mg·kg^-1),罗格列酮阳性对照组(3 mg·kg^-1)。另取12只正常大鼠设为正常对照组。给药组每天灌胃给药1次,连续给药6周;模型组和正常对照组则给予同体积的生理盐水灌胃。给药6周后,采用葡萄糖氧化酶法测定大鼠的空腹血糖(FBG);放射免疫法测定空腹胰岛素(FINS),并计算胰岛素敏感指数(ISI);酶联免疫法测定大鼠的甘油三酯(TG)、总胆固醇(TCH)、游离脂肪酸(FFA)和糖化血红蛋白(GHb);果糖胺法测定糖化血清蛋白(GSP);Western blotting检测脂肪组织过氧化物酶体增殖物激活受体γ(PPARγ)的表达情况。结果: 与正常对照组相比,糖尿病模型组血脂、FBG以及GHb显著升高,FINS及ISI显著下降,脂肪细胞PPARγ蛋白表达水平降低。与模型组相比,TTPGL中、高剂量组大鼠的FBG和GSP显著降低,FINS以及ISI显著升高,脂肪组织PPARγ蛋白的表达水平升高(P<0.01或P<0.05);此外,TTPGL能显著降低糖尿病大鼠血脂水平,TG、TCH和FFA含量均明显降低(P<0.01或P<0.05)。结论: TTPGL能显著降低2型糖尿病大鼠的血糖和血脂水平,明显改善糖尿病动物的糖脂代谢紊乱,升高血清胰岛素水平,提高胰岛素敏感指数;其抗糖尿病作用机制可能与其增加PPARγ蛋白的表达有关。