Blockade of the NMDA receptor increases developmental apoptotic elimination of granule neurons and activates caspases in the rat cerebellum

Elimination of neurons produced in excess naturally occurs during brain development through programmed cell death. Among the many survival factors affecting this process, a role for neurotransmitters acting on specific receptors has been suggested. We have performed an in vivo pharmacological blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, using the competitive NMDA receptor antagonist CGP 39551 at developmental stages corresponding to those at which a survival dependence on the stimulation of this receptor has been demonstrated for cerebellar granule neurons explanted in culture (typically from postnatal day 7 to postnatal day 11 or 13). We were able to demonstrate an increased level of DNA fragmentation in the cerebellum of the treated rats. At the P11 stage, in particular, the fragmented DNA extracted from the cerebellum of CGP 39551-treated pups showed a clear laddering of nucleosomal fragments after agarose-gel electrophoresis. Accordingly, in situ TUNEL technique showed a remarkable increase of cells positive for nucleosomal DNA fragmentation, particularly in the inner granular layer of the cerebellum of treated rats at P11 stage. Therefore, the natural rate of apoptotic elimination of cerebellar granule neurons is considerably enhanced under conditions of pharmacological blockade of the NMDA receptor, thus demonstrating, for the first time in vivo, a clear survival dependence of these neurons upon the stimulation of the NMDA receptor. Concomitantly with the increased rate of apoptotic elimination of granule neurons, the activity of two death proteases of the caspase family, in particular of caspase 3 and caspase 1 at a lower extent, was remarkably increased in the cerebellum of the treated rats. On the contrary, a marker related to the normal differentiation process of granule neurons, the enzyme ornithine decarboxylase, was strongly decreased in its activity in the cerebellum of treated rat pups.     

辛芩冲剂治疗变应性鼻炎的疗效和安全性分析

目的：探讨辛芩冲剂对变压性鼻炎的疗效和安全性。方法：确诊为变应性鼻炎的患者142例随机分成两组，试验组（112例）接受辛芩冲剂口服，一次5g，一日3次；对照组（30例）接受千柏鼻炎片口服，一次3片，一日3次，二种药物均用药20天。观察的症状包括喷嚏、流涕、鼻塞和鼻痒，并进行4分法评分，计算出治疗后积分改善率。结果：经过20天的治疗，辛芩冲剂治疗组的临床控制率为27．67％（31／112），显效率为43．75％（49／112），有效率为17．86％（20／112），无效率为10．71％（12／112），总有效率为89．29％（100／112）；千柏鼻炎片治疗组的临床控制率为0％（0／30），显效率为6．67％（2／30），有效率为20．00％（6／30），无效率为73．33％（22／30），总有效率为26．67％（8／30）。经统计学处理两者差异有显著性意义（P＜0．01），辛芩冲剂治疗组明显优于千柏鼻炎片治疗组，辛芩冲剂和千柏鼻炎片治疗组的病人均未发生不良反应。结论：辛芩冲具有疗效好、无毒副作用等优点，是治疗变应性鼻炎的理想药物。     

微细药物表面包覆技术在制剂中的应用

新型药物开发制备过程中，需要对药物颗粒进行粒子设计，通过多层微胶囊化而得到复合包覆药物颗粒。药物包覆、微胶囊制备方法很多，可分为化学法、物理化学法、物理法。本文着重介绍了制备复合多层包覆药物颗粒的几种物理机械方法：复合杂化系统，高速椭圆转子混合法、喷流床包覆法。简要分析了该技术用于中药现代化加工的可能性。     

柴蔻冲剂对慢性酒精性肝损伤大鼠抗脂质过氧化作用的实验研究

观察中药复方柴蔻冲剂（ＣＫＩ）对慢性酒精性肝损伤大鼠的防护作用。ＣＫＩ可显著提高红细胞和肝组织中超氧化物歧化酶（ＳＯＤ）活性，血与肝组织中过氧化氢酶（ＣＡＴ）、谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）的活性。显著降低血浆与肝组织中脂质过氧化终产物丙二醛（ＭＤＡ）含量，抑制氧自由基的产生，提高组织抗氧化能力。并探讨了柴蔻冲剂的量效关系。     

养血清脑颗粒治疗老年期痴呆的临床疗效观察

目的：观察养血清脑颗粒对老年期痴呆的疗效。方法：治疗组老年期痴呆患者36例均应用养血清脑颗粒。详录治疗前后实验室检查数据。健康老年人34例为对照组，以其体检时所得相关指标与治疗组比较分析。结果：有效率85％，S-TC明显下降，P-SOD明显升高，P-LPO，Ht，Va降低、EET缩短。结论：养血清脑颗粒具有降脂、抗自由基损伤。改善异常血液流变，增加脑血流量等功用。对老年期痴呆防治有较好效果。     

心安颗粒对正常小鼠血清抗体的作用

目的观察心安颗粒对正常小鼠血清抗体的作用。方法KM小鼠用药后,浊度法检测血清IgA、IgG、IgM。结果心安颗粒使血清IgA、IgG、IgM升高(P<0.05),大、中剂量组与黄芪精作用相当,试药组间有量效关系。结论心安颗粒可增强正常小鼠体液免疫功能。     

Dexamethasone induces TrkA and p75NTR immunoreactivity in the cerebral cortex and hippocampus

Nerve growth factor (NGF) plays a crucial role in synaptic plasticity during brain development and adulthood by activating a dual receptor system composed of TrkA and p75 (p75NTR) receptors. Exogenous NGF modulates the expression of both receptors. Little is known about the ability of endogenous NGF to regulate the expression of these receptors in basal forebrain cholinergic terminals. The ability of glucocorticoids to increase NGF expression in the hippocampus prompted us to investigate whether the synthetic glucocorticoid dexamethasone (DEX) increases TrkA and p75NTR expression in NGF-target cholinergic neurons in developing rats. We first examined the effect of DEX on NGF mRNA by in situ hybridization. DEX given systemically (0.5 mg/kg, sc) for 1 week to 7-day-old rats elicited an increase in NGF mRNA levels in the dentate gyrus of the hippocampus and superficial layers II and III of the cerebral cortex. Immunohistochemical analysis of p75NTR and TrkA levels revealed a dramatic increase in p75NTR immunoreactivity (IR) in both basal forebrain and hippocampus and TrkA IR in the hippocampus. Interestingly, in DEX-treated rats more axonal terminals were immunopositive for p75NTR in the hippocampus and cortex, suggesting an increase in p75NTR IR in cell bodies as well as in terminals. Our data indicate that the endogenously produced NGF elicits biological changes similar to those of the exogenously delivered NGF. We suggest that glucocorticoids might regulate and coordinate cholinergic neuronal maturation by increasing the biosynthesis of NGF.     

无糖型腰痹康颗粒工艺研究

目的 优选无糖型腰痹康颗粒剂的成型工艺.方法 以制剂成型率、吸湿率为筛选指标,筛选出其处方中加入辅料的品种、配比及其最佳的成型工艺.结果 1份腰痹康颗粒的稠膏加入3倍量的糊精为最佳处方.结论 优选的工艺可行,颗粒的抗湿性、成型性能均良好.     

稳心颗粒在治疗心律失常中的优势

经过多年实验研究及临床应用,稳心颗粒的抗心律失常作用得到了证实,药理研究表明稳心颗粒可推迟心律失常的出现时间,缩短心律失常持续时间;通过全细胞膜片钳技术研究结果提示,稳心颗粒的甘松提取液对心肌细胞膜的离子通道有抵制作用。稳心颗粒作为中药组方,对功能性心律失常、老年及儿童心肌炎患者伴发的心律失常均有良好的疗效。     

Shugan granule contributes to the improvement of depression‐like behaviors in chronic restraint stress‐stimulated rats by altering gut microbiota

AimThe investigation aims to evaluate the potential effect of Shugan Granule (SGKL) on the gut, brain, and behaviors in rats exposed to chronic restraint stress (CRS).MethodsThe fecal microbiota and metabolite changes were studied in rats exposed to CRS and treated with SGKL (0.1 mg/kg/day). Depressive behaviors of these rats were determined through an open‐field experiment, forced swimming test, sucrose preference, and weighing. Moreover, LPS‐stimulated microglia and CRS‐stimulated rats were treated with SGKL to investigate the regulation between SGKL and the PI3K/Akt/pathway, which is inhibited by LY294002, a PI3K inhibitor.Results(i) SGKL improved the altered behaviors in CRS‐stimulated rats; (ii) SGKL ameliorated the CRS‐induced neuronal degeneration and tangled nerve fiber and also contributed to the recovery of intestinal barrier injury in these rats; (iii) SGKL inhibited the hippocampus elevations of TNF‐α, IL‐1β, and IL‐6 in response to CRS modeling; (iv) based on the principal coordinates analysis (PCoA), SGKL altered α‐diversity indices and shifted β‐diversity in CRS‐stimulated rats; (v) at the genus level, SGKL decreased the CRS‐enhanced abundance of Bacteroides; (vi) Butyricimonas and Candidatus Arthromitus were enriched in SGKL‐treated rats; (vii) altered gut microbiota and metabolites were correlated with behaviors, inflammation, and PI3K/Akt/mTOR pathway; (viii) SGKL increased the LPS‐decreased phosphorylation of the PI3K/Akt/mTOR pathway in microglia and inhibited the LPS‐induced microglial activation; (ix) PI3K/Akt/mTOR pathway inactivation reversed the SGKL effects in CRS rats.ConclusionSGKL targets the PI3K/Akt/mTOR pathway by altering gut microbiota and metabolites, which ameliorates altered behavior and inflammation in the hippocampus.