金双歧联合有氧运动对老年腹泻型肠易激综合征患者的效果

【摘要】 目的 探讨双歧杆菌乳杆菌三联活菌片(金双歧）联合有氧运动对老年腹泻型肠易激综合征（Diarrhea Irritable Bowel Syndrome,IBS D）患者的效果。方法 将2017年1月～2018年10月在本院接受诊治的老年IBS-D患者按照随机数字表法分为对照组和观察组,每组各86例。对照组患者接受金双歧治疗,2 g/次,3次/天,连续12周。观察组患者在对照组的基础上进行有氧运动,5次/周,连续12周。比较两组患者的症状评分、治疗效果、血清P物质（Substance P,SP）、神经肽Y（Neuropeptide Y,NPY）、肿瘤坏死因子α（Tumor Necrosis Factor α,TNF-α）和白细胞介素 6（Interleukin 6,IL-6）水平以及汉密尔顿抑郁量表（Hamilton Depression Scale,HAMD）和汉密尔顿焦虑量表（Hamilton Anxiety Scale,HAMA）评分。 结果 经过12周的治疗后,观察组患者的腹痛、腹胀、大便性状、排便频率、HAMD和HAMA评分明显低于对照组,差异均有统计学意义（P＜0.05）;观察组总有效率为91.86%,对照组总有效率为73.26%,两组的差异有统计学意义（P＜0.001）;观察组患者的血清NPY水平明显高于对照组,SP、TNF-α和IL-6水平明显低于对照组,差异均有统计学意义（P＜0.05）。结论 金双歧联合有氧运动通过调控SP和NPY释放,减轻炎症状态而协同改善老年IBS-D患者的临床症状以及抑郁、焦虑情绪,治疗效果优于金双歧单一治疗。     

Ultrastructural localization of neuropeptide Y-immunoreactivity in the axonal reticulum elements, accumulating anterogradely in transected rat sciatic nerve

The detection of dopamine-β-hydroxylase and cytochrome B561 on the membranes of the axonal reticulum demonstrated that in sympathetic neurons the different compartments of the axonal reticulum participate in the formation of neurosecretory vesicles. In the present study we tried to reveal that the components of the vesicular content are also channeled along the axonal reticulum, by examining whether neuropeptide Y could be localized in elements of the axonal reticulum. Therefore 6 h transected rat sciatic nerve was embedded in glycolmethacrylate and an immunogold labeling was performed. Counterstaining with phosphotungstic acid at low pH selectively contrasted the accumulated axonal reticulum elements and associated granules. In the non-myelinated axons gold labeling was localized on granules and on tubular and granular profiles, demonstrating the presence of neuropeptide Y in the accumulated axonal reticulum elements. This indicates that neuropeptides are indeed transported via the axonal reticulum to the nerve ending and suggests that the accumulation of large dense-cored vesicles at a block is mainly due to local new formation rather than down transport.     

Reserpine-induced effects in the adrenergic neuron as studied with cytofluorimetric scanning

The anterograde axonal transport of norepinephrine (NE), dopamine-β-hydroxylase (DBH), neuropeptide Y (NPY) and tyrosine hydroxylase (TH) was studied in the rat sciatic nerve after reserpine (10 mg/kg). The histochemical method of Hillarp and Falck was used to study NE and the indirect immunofluorescence technique to study DBH-, NPY- and TH-immunoreactive material (IR), using antisera produced in rabbits. The rats were given reserpine 18 hr, or 1–7 days before sacrifice. Before perfusion fixation one nerve was dissected, frozen and freeze-dried for studies on NE, and the contralateral nerve was then processed for immunofluorescence. The amount of fluorescent material accumulated proximal to a 12 hr crush was quantified in longitudinal sections of the nerve using a cytofluorimetric scanning method. During the early phase after reserpine (18 and 25 hr) the amounts of accumulated NE were undetectable or very low, near control levels at 2 day, and overshooting to 160% of control at 4 d after reserpine. Accumulations of DBH-IR, NPY-IR and TH-IR were also depressed initially to 60–70% of control. DBH-IR and TH-IR thereafter increased to supranormal levels (140% of control) at day 4, while NPY-IR did not exhibit any overshooting but accumulated in the normal range at 2, 4, and 7 days. The results indicate that the amount of material transported distally early after reserpine is depressed. After local vinblastine-treatment of the lumbar sympathetic ganglia the amounts of DBH-IR and TH-IR in the perikarya were markedly lower in reserpine treated rats than in controls, probably due to a decreased perikaryal synthesis of these two enzymes. Rectal temperature in these rats decreased during the initial 10 hr after reserpine by up to 3°C. Thus, the decreased synthesis may be caused by the lowered body temperature, which also may slow down the rate of anterograde axonal transport. The later overshooting in accumulated amounts of NE, DBH-IR an TH-IR gives support to the hypothesis that amine granules containing DBH and NE are produced and transported in supranormal amounts around the 4th day after reserpine. Also, the results indicate that a considerable fraction of TH-IR is transported with organelles, probably amine storage granules, in adrenergic axons. NPY, shown to be localized in amine storage granules, did not overshoot at day 4 after reserpine, in contrast to DBH-IR, TH-IR and NE. We suggest that the induction in perikaryal synthesis, triggered by reserpine, is restricted to mRNA coding for DBH and TH, while, mRNA coding for NPY is not induced. This may imply an altered biochemical composition (less NPY/DBH) of the amine granules in transit distally around day 4 after reserpine in rat adrenergic axons.     

缬沙坦对原发性高血压左心室肥厚者血浆神经肽Y的影响

目的:研究神经肽Y(NPY)与原发性高血压(EH)和左心室肥厚(LVH)的关系及探讨缬沙坦降压和逆传LVH的机制。方法:对比观察EH伴LVH者(HHD组)和不伴LVH者(EH组)左室心肌重量指数(LVMI)及皿浆NPY浓度,并对二者进行相关分析,将40例HHD患者随机分为缬沙坦组(VAL组20例)和肼苯哒嗪组(HYD组20例)观察治疗前与治疗12周后LV-MI和NPY的变化。结果:HHD组LVMI和NPY均明显高于EH组,二组间血压无显著差异,LVMI与NPY吴正相关关系(y=0.63,P<0.05),VAL组与HYD组治疗后血压均下降,二者降压效果不差异(P>0.05),VAL组LVMI及NPY均降低,差异有显著性(P<0.05),而HYD组治疗后LVMI及NPY未见明显变化(P>0.05)。结论:NPY在LVH形成过程中起一定作用,缬沙坦降压及逆转LVH机制部分源于对NPY释放的影响。     

大鼠运动训练与限制活动对血浆神经肽Y、儿茶酚胺浓度及其应激改变的影响

大鼠游泳训练与限制活动8周后测定安静与衰竭游泳运动后血浆神经肽Y(NPY)、去甲肾上腺素(NE)、肾上腺素(E)的浓度。结果说明,由于NPY、NE、E的合成、贮存、释放不完全一致,同时测定NPY、NE和E反映运动对交感神经系统兴奋性的影响将更有意义,也更全面。     

Intracerebroventricular Administration of NPY Increases Sympathetic Tone Selectively in Vascular Beds

NPY is widely distributed and has broad regulatory actions in the peripheral and central nervous system (CNS) and is especially important in the regulation of cardiovascular responses. CNS administered NPY has been demonstrated to produce both increases and decreases in cardiovascular tone. In this study we evaluated the effect of intracerebroventricular (ICV) administered NPY on cardiovascular tone, regional blood flow dynamics, as well as the mechanism of this action in normal animals. Male rats were instrumented with ICV cannulas and allowed to recover. At the time of the experiment the rats were anesthetized with urethane/chloralose and the femoral artery cannulated for blood pressure determinations. The abdomen was opened and Doppler flow probes were placed around the iliac, renal, and superior mesenteric artery. Mean arterial pressure (MAP), heart rate (HR), iliac, renal, and superior mesenteric flow, as well as the calculated iliac, renal, and superior mesenteric conductance were determined. ICV administered NPY resulted in an increase in MAP and HR, which was associated with decreased flows in the iliac and superior mesenteric vessels while increasing renal flow. Conductance was decreased in the iliac and superior mesenteric vascular beds but not the renal artery. ICV administration of NPY in the presence of a systemically administered α₁-adrenergic inhibitor, prazosin, attenuated the NPY-mediated effects on MAP as well as vascular conductance in the iliac and superior mesenteric vessels. Additionally, ICV administration of NPY in the presence of a systemically administered β₁-adrenergic inhibition, atenolol, also attenuated the NPY-mediated increase in HR and MAP. Blood flow responses and iliac and superior mesenteric vascular conductance were also attenuated by atenolol pretreatment. In these studies we conclude that lateral ventricular administration of NPY acts to increase systemic MAP and HR and the response is mediated by an increase in sympathetic tone to the heart and especially the splanchnic and skeletal muscle vasculature.     

助胃膏结合推拿治疗脾胃虚弱型小儿厌食症的临床观察

目的:探讨助胃膏结合推拿对厌食症患儿的体重、体质指数(body mass index,BMI),血清中微量元素钙、铁、锌、血红蛋白,食欲调节因子促食欲激素/瘦素(Ghrelin/Leptin),神经肽Y(NPY),中医临床证候积分的变化及临床疗效。方法:选取1~7岁符合诊断标准的患儿94例,随机分为治疗(助胃膏结合推拿)组与对照(健胃消食口服液)组,各47例。治疗组口服助胃膏3次/日,1丸/次,连续6日为1疗程,共治疗2个疗程;推拿1次/日,连续6日为1疗程,疗程间隔2日,共治疗2个疗程。对照组口服健胃消食口服液,按年龄服用,1岁以下5 m L/次,2次/日;5岁以上每次10 m L,3次/日;余者每次10m L,2次/日。观察两组治疗前后体重,BMI,血清中微量元素钙、铁、锌、血红蛋白,Ghrelin/Leptin,中医临床证候积分变化及临床疗效。结果:治疗组总有效率为87%,高于对照组总有效率的70%(P0.05),助胃膏结合推拿可有效改善患儿体重,BMI,血清中微量元素,血红蛋白,食欲调节因子Ghrelin/Leptin值,NPY水平,且疗效优于对照组(P0.05)。结论:助胃膏结合推拿可有效改善患儿的食欲状况,疗效优于常规中成药。     

Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet

Diets high in fat or protein and extremely low in carbohydrate are frequently reported to result in weight loss in humans. We previously reported that rats maintained on a low-carbohydrate-high fat diet (LC-HF) consumed similar kcals/day as chow (CH)-fed rats and did not differ in body weight after 7 weeks. LC-HF rats had a 45% decrease in POMC expression in the ARC, decreased plasma insulin, and increased plasma leptin and ghrelin. In the present study we assessed the effects of a low-carbohydrate-high-protein diet (HP: 30% fat, 65% protein, and 5% CHO) on body weight, caloric intake, plasma hormone levels and hypothalamic gene expression. Male rats (n=16) were maintained on CH or HP for 4 weeks. HP rats gained significantly less weight than CH rats (73.4+/-9.4 and 125.0+/-8.2 g) and consumed significantly less kcals/day (94.8+/-1.5 and 123.6+/-1.1). Insulin was significantly reduced in HP rats (HP: 1.8+/-0.6 vs. CH: 4.12+/-0.8 ng/ml), there were no differences between groups in plasma leptin and plasma ghrelin was significantly elevated in HP rats (HP: 127.5+/-45 vs. CH: 76.9+/-8 pg/ml). Maintenance on HP resulted in significantly increased ARC POMC (HP: 121+/-10.0 vs. 100+/-5.9) and DMH NPY (HP: 297+/-82.1 vs. CH: 100+/-37.7) expression compared to CH controls. These data suggest that the macronutrient content of diets differentially influences hypothalamic gene expression in ways that can affect overall intake.     

深低温降低缺血大鼠大脑MMP-9和NPY蛋白水平

目的探讨深低温对缺血大鼠大脑额叶皮质基质金属蛋白酶-9(MMP-9)和神经肽Y(NPY)表达的影响及其保护机制。方法将大鼠随机分为对照组、常温和深低温停循环组,建立大鼠闭式体外循环模型。对照组大鼠正常体温继续体外循环10 min;常温缺血组停循环10 min;深低温缺血组则将体温保持在18.5℃~20℃,停循环10 min。快速断颈取脑,干湿法测定各组脑含水量;取额叶皮质行免疫组化和Western blot检测MMP-9和NPY蛋白表达并计算各组神经元存活率。结果常温缺血组脑含水量明显高于深低温缺血组及对照组,而神经元存活率则明显低于其他两组(P<0.05)。MMP-9在常温组和深低温组的表达明显高于对照组(P<0.05),而在深低温组中的表达明显低于常温组(P<0.05);NPY在常温组和深低温组的表达低于对照组(P<0.05),而在深低温组的表达远高于常温组(P<0.05)。结论深低温通过减少NPY的下降幅度及减少MMP-9蛋白水平,提高神经元的存活率。     

Hypothalamic peptides as drug targets for obesity

The importance of the melanocortin system in obesity has been confirmed by the recent discovery of mutations in the melanocortin MC4 receptor in morbidly obese patients and the finding that intranasal administration of a fragment of melanocortin decreases body fat in humans. Transgenic mice overexpressing melanin-concentrating hormone (MCH) are obese and a second MCH receptor has been identified. In addition, ghrelin, endocannabinoids and glucagon-like peptide 2 have been identified as potentially important central regulators of food intake.