CD4+CD25+调节性T细胞在再生障碍性贫血中的表达及意义

目的:探讨再生障碍性贫血(再障)患者治疗前、后外周血T淋巴细胞亚群、CD4+CD25+T细胞的变化及其临床意义.方法:采用流式细胞术检测23例再障患者治疗前、后外周血T淋巴细胞亚群、CD4+CD25+T细胞的比例,并与健康对照组进行比较.结果:(1)再障患者治疗前CD4+,CD4+/CD8+,CD4+CD25+明显低于健康对照组(P＜0.01),CD8+细胞则明显升高(P＜0.05);重型再障组与慢性再障组比较CD4+CD25+降低,但差异不显著(P＞0.05),CD3+,CD4+,CD4+/CD8+,CD4+CD25+无统计学意义.(2)再障患者治疗后与治疗前相比,CD4+,CD4+/CD8+,CD4+CD25+明显升高(P＜0.01).(3)再障患者治疗有效者与无效者比较CD4+,CD4+/CDs+,CD4+CD25+明显升高(P＜0.01).结论:再障患者存在T淋巴细胞亚群的失调及CD4+CD25+T淋巴细胞的异常表达,且检测外周血T淋巴细胞亚群、CD4+CD25+T细胞有助于了解再障患者的免疫状态、疗效评价及预后判断.     

肾虚大鼠子宫内膜容受障碍免疫学机制的研究

目的建立肾虚型子宫内膜容受障碍大鼠模型,探讨其容受障碍的免疫学机制。方法以羟基脲建立肾虚型大鼠模型,比较模型大鼠与正常雌性大鼠动情期外周血自然杀伤（NK）细胞CD56＋CD16＋、CD56＋CD16、CD56CD16＋亚群水平,白细胞介素-2（IL-2）、白血病抑制因子（LIF）水平,以及内膜IL-2、LIF、各亚群NK细胞表达。大鼠羟基脲造模后妊娠第11天,比较其与正常妊娠大鼠外周血NK细胞、IL-2和LIF的量,以及蜕膜中IL-2、LIF、各亚群NK细胞表达。结果模型组大鼠外周血CD56CD16＋较正常大鼠明显增加、CD56＋CD16/CD56CD16＋明显减少（P〈0.05）;内膜CD56＋CD16＋、CD56＋CD16均明显减少（P〈0.05）,LIF明显减少（P〈0.05）;造模大鼠妊娠后,蜕膜LIF较正常妊娠大鼠明显减少（P〈0.05）。结论羟基脲致肾虚型大鼠模型子宫内膜容受障碍,其致病机制是全身和局部免疫功能异常,可影响妊娠结局。     

活血抗生滴丸对AA大鼠的抗炎与免疫调节作用

目的探讨活血抗生滴丸对佐剂型关节炎(AA)大鼠炎症和免疫功能的影响。方法建立Wistar大鼠AA模型,随机分为5组:活血抗生滴丸0.63、1.25、2.5g/(kgd)剂量组、环孢素A10mg/(kgd)组及模型组。于造模的第19天开始给药,1次/d,连续灌胃30d。检测各组大鼠关节肿胀度以及脾脏、胸腺指数和外周血中免疫球蛋白IgG、IgM、IgA及T淋巴细胞亚群含量。结果活血抗生滴丸2.5g/(kgd)组和环孢素A组能明显降低AA大鼠关节肿胀度,降低脾脏、胸腺指数,降低外周血中IgG含量,减少CD4+细胞数,升高CD8+细胞数,降低CD4+/CD8+比值(P<0.01)。结论活血抗生滴丸可抑制AA大鼠炎症发展,对其体液免疫及细胞免疫均有一定抑制作用。     

肠道病毒71型感染致手足口病患儿外周血B细胞及T淋巴细胞亚群的检测价值

目的:探究肠道病毒71型感染致手足口病患儿外周血B细胞及T淋巴细胞亚群的检测价值。方法:回顾性分析某院40例EV71型HFMD患儿的临床资料。依据是否有合并症分为重症组(20例)及普通组(20例),同时选取同时期于某院体检的20例健康儿童作为对照组,比较3组儿童外周血B细胞及T淋巴细胞亚群CD4^+、CD8^+、CD3^+、CD19^+、CD56^+百分数。结果:重症组外周血B细胞、CD19^+较普通组及对照组显著较高,CD56^+、CD3^+、CD4^+、CD8^+较普通组及对照组显著较低(P<0.05)。结论:EV71型HFMD患儿的外周血B细胞及T淋巴细胞亚群变化显著异常,且随着病情的加重,该变化幅度加大。     

生脉注射液对多发伤患者细胞免疫功能的调节作用

目的:探讨生脉注射液对多发伤患者细胞免疫功能的影响。方法:42例多发伤患者随机分为常规组和生脉组,各21例。常规组采用常规基础治疗,生脉组在常规治疗基础上加用生脉注射液。于治疗前及治疗后第14天测定外周血T淋巴细胞亚群CD4+、CD8+、干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)。另外,治疗后42例多发伤患者(多发伤组)与21例健康志愿者(健康对照组)进行外周血T淋巴细胞亚群、IFN-γ和IL-4比较。结果:多发伤组外周血CD4+、CD8+、CD4+/CD8+比值、IFN-γ及IFN-γ/IL-4比值较健康对照组降低,差异有统计学意义(P<0.01);IL-4较健康对照组升高,差异有统计学意义(P<0.01)。治疗后14d,生脉组CD4+、CD4+/CD8+比值、IFN-γ、IFN-γ/IL-4比值较常规组升高,差异有统计学意义(P<0.05或P<0.01);IL-4的表达较常规组降低,差异有统计学意义(P<0.01)。结论:生脉注射液能够改善多发伤患者细胞免疫功能的紊乱状态。     

喘可治注射液对大鼠抗炎和免疫调节机制的研究

目的:探讨喘可治注射液治疗支气管哮喘(简称哮喘)的作用机制.方法:60只雄性Wistar大鼠随机分为正常组、模型组、地塞米松组(0.5 ml·kg-1 ·d-1,肌内注射),高、中、低剂量(10、5、2.5 ml·kg-1·d-1,腹腔注射)喘可治注射液组.以2％卵蛋白为激发液,雾化吸入致敏,建立哮喘模型.治疗后,大鼠肺叶经HE染色后行病理切片,采用酶联免疫吸附(ELISA)法分别测定大鼠外周血中白介素-4(IL-4)和γ-干扰素(IFN-γ)浓度,采用流式细胞仪测定大鼠外周血中CD4+ CD25+T调节细胞和CD3- CD161a+自然杀伤(NK)细胞占淋巴细胞的百分比.结果:各剂量喘可治注射液组大鼠肺叶局部炎症反应均较模型组轻,IL-4浓度均明显下降,与模型组相比差异有显著性(P＜0.01),但各治疗组间、治疗组和正常组间IL-4浓度无显著差异.各治疗组IFN-γ的浓度均较模型组有所上升,其中高剂量组上升最为明显,与模型组比较有显著差异(P＜0.01).高、中、低剂量喘可治注射液组CD4+ CD25+T调节细胞百分比均明显上升,与模型组相比有显著差异(P＜0.05).CD3- CD161.+ NK细胞的百分比各组间比较无显著性差异.结论:喘可治注射液可增加血中IL-4、IFN-γ浓度,及CD4+ CD25+T调节细胞含量,纠正免疫失衡,这可能是其治疗哮喘的机制之一.     

益气活血颗粒对心气虚证T淋巴细胞亚群影响的实验研究

目的：观察益气活血颗粒对大鼠心气虚证T淋巴细胞亚群的影响。方法制作心气虚证大鼠动物模型,随机分为4组：大、小剂量实验组（2.0,0.5 g/100 g益气活血颗粒）、对照组（1 g/100 g天王补心丸）及空白组,均1次/日,连续7d灌胃,观察各组外周血T淋巴细胞亚群的变化。结果模型组外周血CD3＋、CD4＋低于空白组, CD8＋含量高于空白组,且与各组比较均有显著性差异（P＜0.01）;大剂量实验组与对照组比较有显著性差异（P ＜0.01）。结论益气活血颗粒可升高CD3＋、CD4＋的含量,降低CD8＋含量。     

特发性血小板减少性紫癜患者外周血T淋巴细胞亚群变化及临床意义

目的探讨应用流式细胞检测技术测定特发性血小板减少性紫癜患者外周血中血小板相关免疫球蛋白水平及T淋巴细胞亚群变化情况。方法采用流式细胞仪检测我院25例特发性血小板减少性紫癜患者(观察组),对照组(正常健康者)25例,对两组患者外周血中血小板相关免疫球蛋白水平及T淋巴细胞亚群变化比较分析。结果观察组患者外周血中血小板相关免疫球蛋白水平均明显高于对照组(P0.05);观察组患者的CD3+,CD3+CD4+亚群明显较对照组降低(P0.05),而其CD3+CD8+亚群明显较对照组升高(P0.05),且CD3+CD4+/CD3+CD8+比值显著降低(P0.05)。结论特发性血小板减少性紫癜患者外周血中血小板相关免疫球蛋白水平明显增高,T淋巴细胞亚群变化明显,与该病免疫机制有关。     

急性胰腺炎大鼠外周血淋巴细胞亚群的变化

目的检测急性胰腺炎（ AP）大鼠外周血淋巴细胞亚群,探讨AP病程进展过程中免疫状态改变的原因。方法60只SPF级雄性Wistar大鼠随机分为空白组、假手术组、AP组（ AP 6 h组、12 h组及AP 24 h组）。采用胰腺被膜下注射牛磺胆酸钠（ Na-Tc）建立急性胰腺炎模型。空白组及假手术组在第6小时处死,胰腺炎组在造模后第6、12、24小时3个时点分批处死。每只大鼠处死前腹主动脉抽血5 ml,取胰腺组织行HE染色并做病理评分。测定每只大鼠淋巴细胞计数及血清淀粉酶,用流式细胞仪测定淋巴细胞亚群CD3＋、CD4＋、CD8＋、CD19＋及CD56＋。结果假手术组与空白组比较淋巴细胞无明显降低（ P ＞0构．05）,随着病程的延长CD3＋淋巴细胞逐渐下降,CD8＋淋巴细胞轻度增高,CD4＋/CD8＋明显下降,CD3＋/CD19＋明显上升（ P ＜0．05）。结论在AP病程中免疫系统的紊乱是逐渐加重的。     

骨髓间充质干细胞对再生障碍性贫血免疫损伤修复的影响

目的研究骨髓间充质干细胞(BMSCs)对受体调节性T细胞(T-regs)亚群的作用。方法取C57BL/6(B6)小鼠骨髓,培养BMSCs。体外诱导建立再生障碍性贫血(AA)小鼠模型,实验组(10只)于制模后第9天注射BMSCs,对照组(10只)未予处理。注入BMSCs后第5天,取血动态观察CD4+T-regs亚群、CD8+T-regs亚群及小鼠外周血象变化。结果成功培养出BMSCs,并建立AA模型。与对照组相比,实验组注射BMSCs后第5天的血象未出现继续下降,第14天时造血已基本恢复。实验组CD4+T-regs和CD8+T-regs亚群均较对照组明显升高(P<0.05)。结论外源性BMSCs注射通过对T-regs的调节,从而促进AA的造血功能恢复。     

Effects of cannabidiol and of diphenylhydantoin on the hippocampus and on learning

Cannabidiol (3.5 mg/kg, i.p.) depressed hippocampal facilitation and posttetanic potentiation of evoked responses in rats, such, as had been reported before for diphenylhydantoin. Both diphenylhydantoin (80 mg/kg, i.p.) and cannabidiol blocked the increase of hippocampal RNA concentration caused by afferent stimulation, and depressed the acquisition of a conditioned avoidance response in rats. Neither drug affected the retention of such response when given by posttrial injection, nor the spontaneous locomotor activity of mice. The effects of both agents may be explained by the interference they have been previously shown to produce with the release of K⁺ from the hippocampus during stimulation. In fact, hippocampal facilitation and posttetanic potentiation and the RNA response to stimulation have been shown to be phenomena which depend on this K⁺ release, and have been attributed a role in learning.     

妊娠合并子宫肌瘤对母儿影响的分析

目的 探讨妊娠合并子宫肌瘤对母儿的影响。方法 对1999年1月～2004年12月73例在剖宫产术中发现的子宫肌瘤进行分析。结果 妊娠合并肌瘤的胎位异常（臂位）率、产后出血率分别为17．8％、20．54％,而对照组分别为3．18％和8．97％;低体重儿发生率12、33％,而对照组为6．07％,有显著差异。结论 子宫肌瘤增加了母儿并发症的可能性;合并黏膜下肌瘤也有望使妊娠过程成功。     

朱砂及含朱砂制剂的肝肾毒性研究

目的 探讨朱砂、含朱砂制剂（柏子养心片）及甲基汞对大鼠的体内外毒性,为其临床安全用药提供科学依据。方法 ①对比甲基汞、朱砂及柏子养心片体外对人肝HL-7702细胞和人肾近曲小管上皮HK2细胞的毒性,计算半数抑制浓度（IC₅₀）。②SD大鼠随机分为对照组,朱砂组0.1 g/kg,柏子养心片0.2、0.4、0.8 g/kg组,甲基汞组0.001 g/kg,每天ig 1次,连续给药90 d后,取血及肝、肾组织;试剂盒法检测血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肌酐（CREA）、尿素氮（BUN）水平,测汞仪固体直接进样法检测肝、肾组织中汞蓄积量,并对大鼠肝脏和肾脏做组织病理学检查。结果 体外试验表明,朱砂、柏子养心片及甲基汞对HL-7702细胞的IC₅₀分别为7.852、6.035、0.009 5 g/L;对HK2细胞的IC₅₀分别为6.297、4.484、0.008 9 g/L。亚慢性毒性试验表明,甲基汞组大鼠肝、肾组织中汞蓄积量及血清中ALT、AST、CREA、BUN值均显著高于对照组,而朱砂及柏子养心片（高、中、低剂量）组与对照组比较均没有显著性差异;甲基汞组大鼠肝脏呈现肝细胞变性,肾脏可见明显肾小管损伤,而朱砂及柏子养心片（高、中、低剂量）组与对照比较没有明显差异。结论 朱砂及柏子养心片的体内外毒性均显著低于甲基汞,在目前药典规定的临床用量下使用安全性较好。     

β3-肾上腺素受体激动剂的研究进展

摘要β     

Effect of ranitidine on ileal myenteric plexus preparation and on acetyl- and butyrylcholinesterase

Ranitidine at concentrations from 1 microM to 0.1 mM brought about a dose-dependent potentiation of the twitch responses elicited by electrical stimulation of the ileal myenteric preparation. At higher concentrations (0.3-3 mM) ranitidine also caused irregular slow contractions of the unstimulated ileal preparation which were potentiated by eserine and blocked by atropine and tetrodotoxin. In order to identify the mechanism of these apparently cholinomimetic actions, the effects of ranitidine on AChE and BuChE were studied. Ranitidine showed an instantaneous and promptly reversible inhibitory action at concentrations between 0.5 and 30 microM. Double reciprocal plots were prepared and equilibrium dissociation constants calculated. It appears that ranitidine exerts an inhibition of the "mixed" type on both AChE and BuChE, but the dissociation constants for BuChE were markedly higher than those for AChE. Since AChE inhibition occurs in the same concentration range potentiating the twitch responses on the ileal myenteric preparation, it may explain the cholinomimetic effect of ranitidine.     

催产素镇痛和抗焦虑药理作用及其机制的研究进展

催产素是由下丘脑合成的一种神经肽,在分娩时促进子宫平滑肌的收缩,但其在社交行为、焦虑、情绪、疼痛调节等方面也起重要作用。催产素通过外周和中枢多种药理机制参与镇痛和抗焦虑的作用已得到广泛研究。综述了近年来催产素与疼痛和焦虑相关的基础和临床研究进展,总结相关作用机制,并进一步探讨了催产素参与的镇痛和抗焦虑间的联系,有助于深入了解其多重作用机制,为这些疾病的治疗及新药研发提供依据。     

Effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on passive and active avoidance behavior and on open-field activity of rats

The action of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on the passive and active avoidance behavior and open-field activity of rats was studied after peripheral and intracerebroventricular administration. When applied before the test session, intracerebroventricular administration increased the avoidance latency of passive avoidance behavior. Subcutaneous, intraperitoneal and intracerebroventricular administration of the peptide delayed the extinction of active avoidance behavior. Both subcutaneous and intracerebroventricula administration increased the grooming activity of the rats. The data suggest that H-Phe-Ile-Try-His-Ser-Tyr-Lys-OH is able to influence memory, acting mainly on the retrieval processes, ad to modify open-field activity.     

Effects of sunitinib and bevacizumab on VEGF and miRNA levels on corneal neovascularization

Aim: To evaluate the effects of sunitinib (0.5?mg/ml) and bevacizumab (5?mg/ml) on VEGF-A, VEGFR-2 and microRNA (miRNA) levels on corneal neovascularization (CNV).

Methods: In this study, CNV was induced by silver nitrate application to the cornea, and 40 Albino male rats were equally divided into four subgroups:

Group 1 (sunitinib): After silver nitrate application to the cornea, 0.5?mg/ml sunitinib eyedrop was administered twice daily for two weeks (n?=?10).

Group 2 (bevacizumab): After silver nitrate application to the cornea, 5?mg/ml bevacizumab eyedrop was administered twice daily for two weeks (n?=?10).

Group 3 (control): After silver nitrate application to the cornea, normal saline eyedrop was administered twice daily for two weeks (n?=?10).

Group 4 (vehicle): After silver nitrate application to the cornea, 1% DMSO eyedrop was administered twice daily for two weeks (n?=?10).

After two weeks from the silver nitrate application, corneas were evaluated by hand-held biomicroscope for their vascularization status. Then, corneas were excised and the expression levels of VEGFR-2, VEGF-A and the common miRNA markers for neovascularization (miR-15?b, miR-16, miR-23a, miR-126, miR-188, miR-210, miR-221, miR-222, miR-410 and miR-423) were evaluated by real-time PCR.

Results: It was seen that the CNV was decreased in sunitinib- and bevacizumab-administered groups compared to the control and DMSO groups. Also, in comparison with the control group; VEGF-A expression was downregulated by nearly 0.75 times in sunitinib group and nearly 0.52 times in bevacizumab group. VEGFR-2 expression was downregulated by 0.89 times in sunitinib group and 0.68 times in bevacizumab group, compared to the control group. miR-15?b, miR-16 and miR-126 levels were statistically lower in sunitinib and bevacizumab groups, but miR-188 and miR-410 levels were two-fold higher compared to the control group. The miR-210 level was found higher only in sunitinib group compared to the control group. There were no statistically significant changes in miR-23a, miR-221, miR-222 and miR-423 levels among the groups.

Conclusion: Topical application of bevacizumab (5?mg/ml) and sunitinib (0.5?mg/ml) decreases the levels of VEGFR-2 and VEGF-A in CNV. Further studies are needed for detailed analysis of genes which are targeted by up- or downregulated miRNAs in this study.     

丹参多酚酸盐治疗不稳定型心绞痛的疗效及其对一氧化氮和内皮素的影响

目的观察丹参多酚酸盐治疗不稳定型心绞痛（UA）的疗效及其对血清一氧化氮（NO）和内皮素（ET）水平的影响。方法 60例患者随机分为治疗组和对照组各30例。对照组给予常规抗心绞痛治疗,治疗组在对照组治疗的基础上加用丹参多酚酸盐注射液。观察比较2组临床疗效、血清NO和ET水平及心电图改善和药物不良反应情况。结果 治疗组临床疗效、血清NO和ET水平及心电图改善情况均优于对照组,差异有统计学意义（P〈0.05）。2组均未发生药物不良反应。结论丹参多酚酸盐可明显改善UA患者的临床症状和心电图ST-T改变,要提高血清NO水平的同时降低ET水平。     

Influence of streptozotocin-induced diabetes on blood pressure and on renin formation and release

Summary I.v. injection of 40 mg/kg or 65 mg/kg streptozotocin reliably induced diabetes in female Sprague-Dawley rats, but failed to induce hypertension within the following 42 days. In most animals injected with the higher dose and in some animals injected with the lower dose, the tail blood flow was permanently impaired so that no blood pressure signals could be obtained by tail plethysmography. This phenomenon occurred also when the drug was injected into the jugular vein and thus was not due to a local effect of streptozotocin. 15 days after 65 mg/kg streptozotocin, the mean arterial pressure of the rats was similar to that of controls, when measured in the awake state (carotid cannula) or under ether anaesthesia. 42 days after streptozotocin, under pentobarbital anaesthesia, the blood pressure was again normal in the animals given 40 mg/kg of the drug and depressed in the animals given 65 mg/kg of the drug 42 days previously. The increase of blood pressure induced by 1 g/kg (–)-noradrenaline i.v. was similar in the latter group of animals and in controls.The renal cortical renin concentration was much lower than in controls 42 days after either dose of streptozotocin, while the plasma renin activity was normal (40 mg/kg) or increased (65 mg/kg). The low renal renin content may have been due to the diabetic state, rather than to the drug itself. Adrenal medullary dopamine-beta-hydroxylase activity was increased 42 days after the higher dose of streptozotocin.Supported by the Swiss National Science Foundation, grant Nr. 3.410.078