野菊花提取物对慢性支气管炎大鼠血清和支气管肺泡灌洗液中TNF-α、IL-6含量及肺组织病理形态学的影响

目的研究野菊花提取物对慢性支气管炎(CB)大鼠血清和支气管肺泡灌洗液(BALF)中TNF-α、IL-6含量以及肺组织病理形态学的影响,探讨其治疗CB的机制。方法制备野菊花提取物;Wistar大鼠随机分为空白对照组,CB模型组,喘息灵对照组,野菊花提取物低、中、高剂量组;气管内注入脂多糖建立CB大鼠模型,药物干预后,ELISA法测定大鼠血清及BALF中TNF-α及IL-6含量,观察肺组织的病理形态学变化。结果模型组大鼠血清及BALF中TNF-α及IL-6含量较空白对照组明显升高,肺组织发生明显病理损伤,野菊花提取物可显著降低上述异常升高的指标、改善肺组织的病理损伤。结论降低CB大鼠体内TNF-α、IL-6含量,改善肺组织的病理损伤,可能是野菊花提取物减轻CB炎症效应机制之一。     

锁阳对衰老模型大鼠脾淋巴细胞转化能力、脾病理学变化及血清SOD、MDA、NO水平的影响

目的 探讨锁阳多糖、水提取物咀嚼片延缓衰老的效应及其作用机制.方法 提取并制备锁阳多糖、水提取物咀嚼片;Wistar大鼠随机分为空白对照组、衰老模型组、维生素E对照组、锁阳多糖组、水提物组,以D-半乳糖建立衰老大鼠模型,药物干预后,MTT法检测各组大鼠脾淋巴细胞对ConA刺激的增殖能力,检测各组大鼠脾脏指数,观察脾组织的病理形态学变化;并检测各组大鼠血清中超氧化物歧化酶(SOD)活性、丙二醛(MDA)及一氧化氮(NO)的含量.结果 与正常组比较,衰老模型组大鼠脾脏指数、脾淋巴细胞对ConA刺激的增殖能力明显下降,脾脏发生明显病理损伤,血清中SOD活性明显下降,MDA及NO含量显著升高(P＜0.05),锁阳提取物咀嚼片能使上述指标明显逆转(P＜0.05).结论 锁阳提取物咀嚼片对D-半乳糖所致衰老模型大鼠脾脏病理变化、脾淋巴细胞免疫功能,自由基代谢相关指标等具有明显改善作用.     

广金钱草提取物对尿石症大鼠肾功能的保护作用

目的研究广金钱草提取物对肾结石大鼠模型的影响,评价其对尿石症大鼠肾功能的保护作用。方法 60只Wistar雄性大鼠分为空白对照组、模型组、低、中、高剂量组,每组10只。空白对照组自由饮水,其余各组给予1%乙二醇+1%氯化铵自由饮水2 w造模。造模成功后广金钱草低、中、高剂量组分别予广金钱草提取物80、160、320 mg·kg~(-1)·d~(-1)灌胃,给药3 w后,测定大鼠24 h排尿量及尿草酸、尿柠檬酸和尿钙(Ca~(2+))、鲜(Mg~(2+));给药4 w后,采取标本,检测血肌酐(Cr)、尿素氮(BUN)、钙Ca2+、磷(P)水平,检测各组大鼠肾脏组织中超氧化物歧化酶(SOD)、丙二醛(MDA)和还原型谷胱甘肽(GSH)水平和肾组织草酸钙结晶沉积及病理变化。结果低、中、高剂量组24 h尿量明显高于空白对照组和模型组(P0.05)。中、高剂量组尿Ca~(2+)明显低于模型组(P0.05),高剂量组尿草酸明显低于模型组(P0.05)。与空白对照组相比,高剂量组尿柠檬酸明显升高(P0.05)。与模型组比较,低、中、高剂量组大鼠血BUN、Cr水平明显下降(P0.05)。低、中、高组GSH、SOD含量显著升高(P0.05),MDA含量明显下降(P0.05)。模型组肾组织内有大量草酸钙晶体形成及沉积,肾小管上皮细胞发生肿胀、变性、坏死显著,管腔扩张,管腔内存在草酸钙晶体沉积,肾间质发生明显的慢性间质性炎症;中、高剂量组肾组织中草酸钙晶体沉积显著减少,结构破坏减轻,管腔扩张程度较轻,病理损伤明显减轻。结论广金钱草提取物对尿石症具有明显的效果,能有效降低模型大鼠血清BUN、Cr,抑制肾组织草酸钙结晶的形成与沉积,保护肾小管细胞,减轻扩张程度,升高GSH、SOD含量水平,降低MDA,减轻肾间质慢性炎症,对肾功能起到保护作用。     

罗格列酮对慢性阻塞性肺疾病大鼠模型肺组织氧化应激的影响

目的探讨罗格列酮对慢性阻塞性肺疾病(COPD)大鼠肺组织氧化应激的影响。方法将健康SD大鼠24只随机分为3组。被动吸烟和气管内滴入脂多糖(LPS)复制COPD大鼠模型,模型组不进行治疗,罗格列酮组灌胃罗格列酮,对照组为正常大鼠。结果制备肺组织匀浆,用试剂盒测定肺组织匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)和一氧化氮(NO)含量。罗格列酮组大鼠肺组织中MDA含量较模型组明显降低,治疗组大鼠肺组织中SOD、NO含量较模型组明显增加。结论过氧化物酶体增生剂激活的受体(PPARγ)激动剂罗格列酮可明显减轻COPD大鼠肺组织的氧化应激反应,并提高其抗氧化能力。     

丹参提取物对放射性肺损伤大鼠的保护作用研究

目的探讨丹参提取物对放射性肺损伤大鼠的保护作用。方法将90只大鼠随机分为3组,每组30只,分别记为A组(正常对照组)、B(单纯照射组)、C(照射加丹参提取物干预组)。A组和B组大鼠给予生理盐水灌胃,C组给予同计量丹参提取物灌胃,同时B组和C组进行X线照射。在X线照射4周、8周、12周后各取10只大鼠心脏采血后处死、取材,检测各组大鼠血清IL-6、TNF-α、TGF-β1水平和SOD活性变化、肺组织MDA含量和NF-κB p65表达及右肺系数。结果相较于A组,B组和C组大鼠照射4周、8周、12周后血清IL-6、TNF-α、TGF-β1水平均明显提高(P0.05),其中C组血清IL-6、TNF-α、TGF-β1水平均明显低于B组,差异有统计学意义(P0.05);相较于A组,B组和C组大鼠各期血清SOD活力明显下降(P0.05),其中C组大鼠各期血清SOD活力明显高于B组(P0.05);相较于A组,B组和C组大鼠照射各期肺组织MDA含量与A组相较有明显提高(P0.05);C组大鼠各期肺组织MDA含量明显低于B组(P0.05);照射4周、8周后,B组大鼠右肺系数明显高于A组和C组(P0.05),12周后各组大鼠右肺系数比较差异无统计学意义(P0.05);相较于A组,B组和C组大鼠各期肺组织NF-κB p65相对表达量有明显提高(P0.05),其中C组大鼠各期肺组织NF-κB p65相对表达量均明显低于B组(P0.05)。结论丹参提取物对放射性肺损伤大鼠保护作用可能是通过降低血清IL-6、TNF-α、TGF-β1水平,提高血清SOD活性水平,降低肺组织织MDA含量、NF-κB p65表达和右肺系数实现的。     

川芎生物碱对大鼠血清中SOD活性、NO、NOS、MDA含量的影响

目的 研究川芎生物碱对局灶性脑缺血再灌注(I/R)大鼠血清中一氧化氮(NO)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量的影响.方法 取大鼠50只,随机分成5组,每组10只.即假手术组,I/R模型组,川芎碱低、中、高剂量治疗组.采用线栓法建立大鼠局造性脑I/R病理损伤模型[1].用黄嘌呤氧化酶法测定血浆中SOD活性;用硫代巴比妥酸显色法测定血浆中MDA含量;用NOS试剂盒测定NOS活性;硝酸还原酶法测定血清中NO含量.结果 I/R组与假手术组相比,血清中的SOD活性降低,MDA含量增加(P＜0.01),川芎碱低、中、高剂量治疗组与I/R组相比,血清中的SOD活性均升高,MDA含量均降低(P＜0.05).I/R组与假手术组相比,血清中NO含量升高,NOS活性增强(P＜0.01),川芎碱低、中、高剂量治疗组与IYR组比,NO含量均显著降低(P＜0.01).结论 川芎生物碱对脑I/R引发的自由基损伤有保护作用,从而减轻脑L/R后脑绢织的损害.     

甘草苷对黄褐斑小鼠模型SOD、MDA、NO含量及黑素瘤A375细胞增殖的影响

目的探讨甘草苷(LQ)对黄褐斑模型小鼠的血清和皮肤中超氧化物歧化酶(SOD)、丙二醛(MDA)活性及一氧化氮(NO)含量及黑素瘤A375细胞增殖作用的影响。方法将60只昆明种雌性小鼠,按体重随机分为空白对照组、模型组、LQ低剂量组(15 mg·kg-1·d-1)、LQ中剂量组(30mg·kg-1·d-1)、LQ高剂量组(60 mg·kg-1·d-1)和维生素C组。空白对照组肌肉注射生理盐水,其余各组肌肉注射黄体酮加紫外线照射法致黄褐斑小鼠模型。各组分别按剂量灌胃给药30 d后,检测小鼠血清和皮肤中SOD、MDA活性和NO含量。用四甲基偶氮唑蓝比色法(MTT)法检测浓度为0.1,1,10μmol/L LQ对黑素瘤A375细胞增殖的抑制作用。结果 LQ高、中剂量组能明显升高黄褐斑模型小鼠的血清和皮肤中SOD活性(P<0.05,P<0.01),降低MDA、NO含量(P<0.05);对A375人黑素瘤细胞增殖有明显的抑制作用(P<0.05)。结论 LQ对黄褐斑模型小鼠有较好的治疗作用,同时抑制黑素瘤A375细胞增殖,其机制可能与增强小鼠机体抗氧化能力、减少氧化物产生、减少黑素细胞形成有关。     

胃炎灵胶囊对慢性萎缩性胃炎模型大鼠氧化-抗氧化平衡的影响

[目的]观察胃炎灵胶囊对慢性萎缩性胃炎(CAG)模型大鼠氧化-抗氧化平衡的影响。[方法]设立空白对照组,并采用综合法复制CAG动物模型32只,随机分为4组,即模型组、胃炎灵大剂量组、胃炎灵小剂量组、维酶素组,每组8只。治疗后分别对各组大鼠胃组织谷胱甘肽-过氧化物酶(GSH-Px)、一氧化氮(NO),胃组织及血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)水平进行检测。[结果]与空白组比较,模型组大鼠胃组织GSH-Px、SOD活性下降(P<0.01),MDA、NO水平升高(P<0.01);血清SOD活性下降(P<0.01),MDA水平升高(P<0.01);与模型组比较,胃炎灵胶囊可提高胃组织GSH-Px、SOD活性(P<0.05,<0.01),降低MDA、NO水平(P<0.01,<0.05),提高血清SOD活性(P<0.05),降低MDA水平(P<0.05),且以胃炎灵胶囊大剂量组作用显著。[结论]胃炎灵胶囊具有提高抗氧化酶活性,减轻自由基损伤和抑制脂质过氧化物反应的作用。     

润肺治纤汤对实验性肺纤维化模型大鼠治疗作用的研究

目的探讨疗效满意的治疗肺纤维化的中药方剂。方法90只大鼠分为5组正常对照组18只;72只气管内滴注博莱霉素复制肺纤维化疾病模型,其中模型组18只,其余54只均分为润肺治纤汤大、中、小剂量中药方剂治疗组。造模后14、28d两个时段处死动物,取肺比较各组大鼠肺系数、肺组织病理学变化、肺组织SOD活性、MDA和羟脯氨酸(Hyp)含量。结果模型组肺组织肺纤维化病理变化明显,肺系数和肺组织MDA、Hyp含量较正常对照组显著增加(P<0.05),SOD活性极显著低于正常对照组(P<0.01);14、28d润肺治纤汤治疗组(大剂量组)肺组织SOD活性与模型组比较显著增加(P<0.05),且有随给药剂量增加而升高趋势,MDA含量与模型组比较显著减少(P<0.05);28d大剂量组肺系数、Hyp含量与模型组比较显著降低(P<0.05)。结论润肺治纤汤对实验性肺纤维化模型大鼠有一定治疗作用。     

全氟化碳对动脉粥样硬化大鼠内皮功能的影响

目的:观察腹腔注射全氟化碳(PFC)对动脉粥样硬化(AS)大鼠血清及主动脉组织一氧化氮(NO)、内皮型一氧化氮合酶(eNOS)、内皮素-1(ET-1)含量的影响,初步探讨PFC对AS大鼠内皮的可能保护作用。方法:将40只Wistar雄鼠随机分为空白对照组、动脉粥样硬化模型组、PFC低剂量组、PFC高剂量组,每组10只。除对照组用普通饲料外,其余均以高脂饲料喂养,建立实验性大鼠AS模型,治疗组在造模的同时给予不同剂量药物干预。12周后,测定各组大鼠血清及主动脉组织eNOS、NO、ET-1的含量,行HE染色观察各组大鼠主动脉病理变化。结果:模型组eNOS、NO含量显著降低,ET-1含量显著升高,与对照组比较有显著差异(P0.05);PFC高剂量组较模型组血清及主动脉eNOS、NO含量显著升高,ET-1含量显著降低(P0.05);PFC低剂量组与模型组相比血清中各指标差异无统计学意义,主动脉组织中ET-1含量显著降低(P0.05);PFC高剂量组与低剂量组相比eNOS、NO含量显著升高,ET-1含量显著降低(P0.05);PFC高剂量组较PFC低剂量组减轻AS大鼠主动脉组织形态学变化更明显。结论:PFC可能通过升高AS大鼠血清及主动脉组织eNOS、NO含量,降低ET-1含量,起到内皮保护功能,发挥抗AS的作用。     

The relation between the effects of hysterectomy, decidual tissue, prolactin, or luteinizing hormone (LH) and the ability of indomethacin to prevent luteolysis in rats bearing LH-dependent corpora lutea

In adult rats hysterectomized on day 8 of pseudopregnancy, the mean serum progesterone (P) level fell from 88 ng/ml on day 8 to 44 ng/ml on day 15 (n = 61). In response to a single sc injection of 0.5 ml of a specific antiserum to LH (LHAS) on day 10, the P level fell to less than 10 by day 15 in 29 of 33 rats; however, this fall, which was indicative of luteolysis, was briefly interrupted by a return to the control level 36 h after treatment. Indomethacin (400 micrograms, sc) administered 12 h before, during, and 12 h after the LHAS injection prevented the luteolysis that followed the 36 h surge in 10 of 15 rats (P less than 0.001). Treatment with 400 micrograms 2Br-alpha ergocryptine (CB 154), sc, on day 10, with or without indomethacin, however, induced a rapid, uninterrupted, and permanent fall to less than 10 in 13 of 13 rats. Treatment with both LHAS and CB 154 reduced the luteolytic effect of CB 154 (P less than 0.001), and indomethacin treatment combined with both LHAS and CB 154 tended to further reduce the luteolytic effect of CB 154 (P less than 0.01). Hypophysectomy on day 10, however, induced rapid, uninterrupted and permanent luteolysis in all rats (15); this was not affected by indomethacin (7 rats) or LHAS (8 rats). Pituitary homotransplantation on day 8 prevented the luteolytic effect of LHAS on day 10 in 6 of 6 rats (P less than 0.003). In decidual tissue (DT)-bearing rats, LHAS on day 10 induced rapid, uninterrupted, and permanent luteolysis in 18 of 18 rats. The response to LHAS on day 10 changed to that of the hysterectomized rat when the DT-bearing uterus was removed on day 8 (12 of 12 rats) or 10 (7 of 7 rats) (P less than 0.001), but did not change when it was removed on day 11 (5 of 5 rats). In DT-bearing rats hysterectomized on day 8, indomethacin in intrabursal Silastic wafers prevented luteolysis in response to LHAS on day 10 (6 of 6 rats; P less than 0.001). Intrabursal indomethacin had no effect on the response to LHAS in intact DT-bearing rats (3 of 3 rats). These results suggest that even when the corpus luteum becomes LH dependent, PRL may retard or prevent LHAS-induced luteolysis in hysterectomized rats. (ABSTRACT TRUNCATED AT 400 WORDS)     

Role of glucocorticoids in the response of the hypothalamo-corticotrope, immune and adipose systems to repeated endotoxin administration.

The present study was designed to determine whether the glucocorticoid inhibitory feedback mechanism plays a role in the well-known tolerance of the neuroendocrine-immune axis response to repeated endotoxemia. Adult male rats underwent adrenalectomy (ADX) and were implanted with a subcutaneous corticosterone (compound B, CB, 75 mg) pellet, or sham operated and implanted with a placebo pellet. On the morning of day 8 after surgery (experimental day, D1), all rats received an intravenous injection of lipopolysaccharide (LPS) (25 microg/kg body weight) which was repeated daily until D5. Blood was drawn via intravenous indwelling catheters before (sample time zero) as well as 1, 2, 3 and 4 h after LPS treatment on D1, 3 and 5 for measurements of corticotropin (ACTH), CB, tumor necrosis factor-alpha (TNF-alpha) and leptin. In sham animals, tolerance to repeated LPS administration was complete by D5 for the corticotrope axis and the immune response. In addition, LPS was found to stimulate leptin secretion on day 1 in intact rats, an effect that also disappeared thereafter. ADX + CB rats showed only a partial tolerance of the corticotrope axis on D5, whereas tolerance of the immune response was similar to that found in sham animals. Interestingly, the acute stimulation of leptin secretion by LPS in ADX + CB rats was qualitatively similar to that of intact controls on D1, but plasma leptin levels were significantly reduced on D3 and 5 compared to controls. Our results demonstrate that the adrenal response tolerance of the hypothalamo-pituitary-adrenal axis to repeated endotoxemia. In addition, our finding that TNF-alpha secretion follows the same pattern in sham-operated and in adrenalectomized animals suggests that unlike the corticotrope axis, tolerance of the immune response does not depend upon stimulated CB levels. The decrease in circulating levels of leptin following ADX is consistent with the stimulatory effects of glucocorticoids on leptin secretion. However, our finding of an acute stimulation of leptin secretion by LPS in ADX + CB animals demonstrates that this effect of endotoxemia is at least partially glucocorticoid independent.     

Carotid body function in aged rats: responses to hypoxia,ischemia, dopamine,and adenosine

The carotid body (CB) is the main arterial chemoreceptor with a low threshold to hypoxia. CB activity is augmented by A₂-adenosine receptors stimulation and attenuated by D₂-dopamine receptors. The effect of aging on ventilatory responses mediated by the CB to hypoxia, ischemia, and to adenosine and dopamine administration is almost unknown. This study aims to investigate the ventilatory response to ischemia and to adenosine, dopamine, and their antagonists in old rats, as well as the effect of hypoxia on adenosine 3′,5′-cyclic monophosphate (cAMP) accumulation in the aged CB. In vivo experiments were performed on young and aged rats anesthetized with pentobarbitone and breathing spontaneously. CB ischemia was induced by bilateral common carotid occlusions. cAMP content was measured in CB incubated with different oxygen concentrations. Hyperoxia caused a decrease in cAMP in the CB at all ages, but no differences were found between normoxia and hypoxia or between young and old animals. The endogenous dopaminergic inhibitory tonus is slightly reduced. However, both the ventilation decrease caused by exogenous dopamine and the increase mediated by A_2A-adenosine receptors are not impaired in aged animals. The bradycardia induced by adenosine is attenuated in old rats. The CB’s peripheral control of ventilation is preserved during aging. Concerns have also arisen regarding the clinical usage of adenosine to revert supraventricular tachycardia and the use of dopamine in critical care situations involving elderly people.     

Bromocriptine-induced changes in the biochemistry, physiology, and histology of the intermediate lobe of the rat pituitary gland

Treatment of rats with 2-Br-alpha-ergocryptine (bromocriptine; CB 154) elicits biochemical, physiological, and histological changes in the intermediate lobe (IL) of the rat pituitary gland, suggesting a decrease in activity in the IL. CB 154 treatment decreases 1) the capacity of the IL to synthesize proopiomelanocortin (POMC), 2) the content of mRNA directing the synthesis of POMC, and 3) the capacity of the IL to synthesize the peptides desacetyl alpha MSH, N,O-diacetyl alpha MSH, and alpha MSH. CB 154 treatment also causes a 40% loss of IL protein and an atrophy of the IL. CB 154 treatment has a biphasic effect upon the IL content of alpha MSH-like peptides; the drug first increases and then diminishes the content of these molecules. Control experiments using CB 154-treated IL tissue suggest that these effects of CB 154 are not a toxic effect of CB 154 on the IL. Spiroperidol reverses the effects of CB 154 on POMC synthesis and POMC mRNA content; by itself, spiroperidol increases the IL synthesis of POMC, the IL content of POMC mRNA, and the capacity of the IL to synthesize immunoreactive alpha MSH. Stalk section of rat pituitary gland also results in an increase in the capacity of the IL to synthesize POMC. These results suggest that a D-2 dopamine receptor mediates a tonic inhibition of the function of the IL.     

Pituitary regulation of corpus luteum progesterone secretion in cyclic rats

Pituitary LH and PRL secretion during the early postovulatory period of the rat estrous cycle seem to affect the corpus luteum (CL) autonomy to secrete progesterone. Thus, while PRL would act luteotropically, LH would be luteolytic. To further investigate these facts, 4-day cyclic rats, treated with either 1 mg bromocriptine (CB) or 0.25 ml 70% ethanol (ETOH) at 1600 h on estrus, were injected with 0.5 ml of either an anti-LH serum (LHAS) or normal horse serum (NHS) at 0800 h on metestrus. Rats treated at 0800 h on metestrus with both, CB and LHAS, were also used. To verify through a different procedure the effect of LH and/or PRL deprivation in estrous cycle CL progesterone secretion, hypophysectomy (HYPOX) and sham HYPOX (SHAM) were done at 0800 h on metestrus in either CB- or ETOH-injected rats at 1600 h on estrus. Hypophysectomized rats at 1600 h on estrus were also used. Progesterone secretion was prolonged up to 0800 h on diestrus in those rats deprived of LH from 0800 h on metestrus (ETOH/LHAS, -/CB + LHAS, ETOH/HYPOX) compared with controls (ETOH/NHS, ETOH/SHAM). This luteotropic effect was absent in those rats lacking estrous afternoon PRL (CB/LHAS, CB/HYPOX, HYPOX/-). No effect on CL progesterone secretion was detected in those rats exclusively deprived of PRL on the afternoon of estrus (CB/NHS, CB/SHAM). These results suggest that in the absence of the protective effects of PRL secretion on the afternoon of estrus, rat CL become extremely sensitive to the luteolytic effects of early diestrous LH levels, and this results in 4-day estrous cycles.     

The effect of anandamide on prolactin secretion is modulated by estrogen

Recent research has revealed that endogenous cannabinoid receptors (CB1 and CB2) react with the active ingredient of marijuana, Delta(9)-tetrahydrocannabinol. Two endogenous ligands activate these receptors. The principal one, anandamide (AEA), activates CB1. AEA and CB1 are localized to various neurons within the brain. Because Delta(9)-tetrahydrocannabinol inhibited prolactin (Prl) secretion following its intraventricular injection into male rats, we hypothesized that AEA would have a similar effect. Estrogen modifies many hormonal responses and is known to increase Prl secretion. Therefore, we hypothesized that responses to intraventricular AEA would change depending on the gonadal steroid environment. Consequently, we evaluated the effects of lateral cerebral ventricular microinjection of AEA (20 ng) into male, ovariectomized (OVX), and estrogen-primed (OVX-E) rats. AEA decreased plasma Prl in male rats, had little effect in OVX females, and increased Prl in OVX-E rats. The results were at least partially mediated by changes in dopaminergic turnover, altering the inhibitory dopaminergic control of Prl release by the anterior pituitary gland. Thus, dopamine turnover was increased in the male rats and decreased significantly in OVX and in OVX-E rats. The changes in Prl may be caused not only by altered dopamine input to the anterior pituitary gland but also by effects of AEA on other transmitters known to alter Prl release. Importantly, in OVX-E rats, the elevated Prl release and the response to AEA were blocked by the AEA antagonist, indicating that AEA is a synaptic transmitter released from neurons that decrease inhibitory control of Prl release.     

Adrenalectomy and experimental hypercorticalism modulate the basal, corticotropin-releasing-hormone- and arginine-vasopressin-stimulated release of hypothalamic beta-endorphin.

Recent in vitro studies have shown that the release of hypothalamic beta-endorphin (beta-END), like that of adenohypophysial origin, is enhanced by both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). However, whereas AVP merely synergizes with CRH in the pituitary, it seems to be essential for the release of hypothalamic beta-END by CRH. The present paper reports on the effects of long-term adrenalectomy (ADX) and subsequent replacement with supraphysiological doses of corticosterone (compound B, CB) upon the in vitro basal and CRH- and AVP-stimulated release of beta-END from the rat hypothalamus. Basal release of beta-END was significantly elevated by ADX, and returned to control levels following CB overdosage. Both ADX and CB replacement significantly reduced the stimulatory effect of CRH (10(-8) M) upon beta-END release. ADX caused no significant change in the AVP (10(-6) M)-induced release of beta-END. However, the AVP-stimulated release of beta-END was completely abolished in ADX rats treated with a high dose of CB. The hypothalamic content of beta-END was also measured following ADX and subsequent CB treatment. Compared with control tissues, those from ADX animals had significantly greater contents of beta-END; the hypothalami from rats with experimentally induced hypercorticalism had markedly reduced concentrations of the opioid peptide. Measurements of basal release and content of AVP in the hypothalamus following long-term ADX and CB treatment revealed that AVP neuronal activity is also subject to manipulations of the glucocorticoid hormone environment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihyperglycemic activity, antihyperlipedemic activity, haematological effects and histopathological analysis of Sapindus mukorossi Gaerten fruits in streptozotocin induced diabetic rats

ObjectiveTo investigate the antihyperglycemic and antihyperlipidemic properties of hydroalcoholic extract of fruits of Sapindus mukorossi Gaerten and its beneficial effect on haematological parameters with histopathological analysis in streptozotocin induced diabetic rats.MethodsSapindus mukorossi fruits extract (250 and 500 mg/kg body weight) and standard drug glybenclamide (0.5 mg/kg body weight) were administered to diabetic rats. Effect of extract on hyperglycemia, hyperlipidemia and hematological parameters was studied in diabetic rats. Histopathological changes in diabetic rat pancreas were also observed after extract and glybenclamide treatment.ResultsDaily oral administration of Sapindus mukorossi fruits extract (250 and 500 mg/kg body weight) and glybenclamide for 20 days showed beneficial effects on blood glucose level (P<0.01) and lipid level. The extract has a favorable effect on the histopathological changes of the pancreas in streptozotocin induced diabetes.ConclusionThese findings reveal that the hydroalcoholic extract of Sapindus mukorossi fruits extract possesses antihyperglycemic and antihyperlipidemic properties. In addition, the extract can prevent various complications of diabetes and improve some haematological parameters.     

Effects of ACTH or hCG on corticosterone and progesterone secretion from adrenal glands of the rats at various ages

Effects of ACTH or hCG on the secretion of corticosterone (CB) and progesterone (PRG) from adrenal glands of the female rats at various ages were studied. In in vitro experiment, adrenal gland cells were isolated from fetal, neonatal, immature and adult rats by the method described by us before and were incubated in MEM. We chose to designate the hormones in the medium as hormone secretion. In in vivo experiment, hormones in the serum were determined. In vitro experiment, in which ACTH was added to the medium, indicated that CB was low in the media containing the cells from fetal and neonatal glands compared to those from immature and adult. PRG was elevated by ACTH addition at all of the ages. hCG addition had no effects on both CB and PRG in the media of immature and adult rats. In vivo experiment, in which ACTH was injected s.c., indicated that the response of serum PRG was slightly earlier than the CB response and peaked with a subsequent decline in immature rats. The results suggest that adrenal gland responds to ACTH from fetal age and secrets PRG, but little of CB in fetal age.     

Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor

The endocannabinoid system has recently been shown to play a role in the regulation of bone metabolism. The type 2 cannabinoid receptor (CB2) has been reported to regulate bone mass, but conflicting results have been reported with regard to its effects on bone resorption and osteoclast function. Here we investigated the role that CB2 plays in regulating bone mass and osteoclast function using a combination of pharmacological and genetic approaches. The CB2-selective antagonist/inverse agonist AM630 inhibited osteoclast formation and activity in vitro, whereas the CB2-selective agonists JWH133 and HU308 stimulated osteoclast formation. Osteoclasts generated from CB2 knockout mice (CB2-/-) were resistant to the inhibitory effects of AM630 in vitro, consistent with a CB2-mediated effect. There was no significant difference in peak bone mass between CB2-/- mice and wild-type littermates, but after ovariectomy, bone was lost to a greater extent in wild-type compared with CB2-/- mice. Furthermore, AM630 protected against bone loss in wild-type mice, but the effect was blunted in CB2-/- mice. We conclude that CB2 regulates osteoclast formation and bone resorption in vitro and that under conditions of increased bone turnover, such as after ovariectomy, CB2 regulates bone loss. These observations indicate that CB2 regulates osteoclast formation and contributes to ovariectomy-induced bone loss and demonstrate that cannabinoid receptor antagonists/inverse agonists may be of value in the treatment of bone diseases characterized by increased osteoclast activity.