山莨菪碱对沙土鼠脑缺血后延迟性神经元死亡的影响

目的　研究山莨菪碱对沙土鼠脑缺血后海马延迟性神经元死亡的影响并探讨其与纹状体多巴胺和 Ａ Ｔ Ｐ 含量变化的关系。方法　制备沙土鼠前脑缺血再灌注模型,脑缺血１０ ｍｉｎ 。３２ 只沙土鼠随机分为假手术组、脑缺血组、脑缺血再灌注组和山莨菪碱组。应用病理检查判断脑缺血后延迟性神经元死亡情况,高效液相测定纹状体 Ａ Ｔ Ｐ 和多巴胺的含量。结果　脑缺血组沙土鼠纹状体 Ａ Ｔ Ｐ 和多巴胺含量明显低于假手术组。在再灌注６０ ｍｉｎ 时,山莨菪碱组沙土鼠纹状体多巴胺和 Ａ Ｔ Ｐ 含量明显高于脑缺血再灌注组［ 多巴胺：（５９ ±１０） ｖｓ （３５ ±１４） ｍｇ·ｋｇ － １ , Ｐ＜ ００１ ; Ａ Ｔ Ｐ：（０８２ ±０１２） ｖｓ （０６２ ±０１０） ｍ ｍｏｌ·ｋｇ－ １ , Ｐ＜ ００５］ 。山莨菪碱组沙土鼠脑缺血后海马 Ｃ Ａ１ 区延迟性神经元死亡数目明显少于脑缺血再灌注组。结论　山莨菪碱可明显减少沙土鼠脑缺血后延迟性神经元死亡数目,机制可能与其减少脑缺血再灌注期间纹状体多巴胺释放和促进 Ａ Ｔ Ｐ 含量恢复的作用有关     

胸腺移植和654—2治疗难治性癫痫的研究

采用胸腺移植和654—2治疗小儿难治性癫痫45例,总有效率达91.1％,明显高于对照组45.2％(P<0.01)。癫痫患儿T细胞亚群测定与对照组比较显示CD_3、CD_4、CD_4/CD_8明显降低(P<0.01),表明癫痫患儿存在细胞免疫功能异常。胸腺移植和654—2治疗后与治疗前比较CD_3、CD_4、CD_4/CD_8明显升高(P<0.01)可达正常水平,表明其能明显改善癫痫患儿的免疫功能。抗癫痫药物治疗前后各免疫学指标无明显改变,甚至降低,表明抗癫痫药物对患儿T细胞亚群变化无明显影响。     

Effect of intracoronary administration of anisodamine on slow reflow phenomenon following primary percutaneous coronary intervention in patients with acute myocardial infarction

Background Many basic and clinical studies have proved that anisodamine can produce significant effect on relieving microvascular spasm, improving and dredging the coronary microcirculation. It may be beneficial to the improvement of slow-reflow phenomenon (SRP) following percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). So we investigated the effect of intracoronary administration of anisodamine on SRP of infarct related artery (IRA) following primary PCI in patients with ST segment elevated acute myocardial infarction (STEAMI). Methods Twenty-one patients with SRP from a total of 148 STEAMI patients accepted primary PCI were enrolled into this study from September 2004 to December 2005. When SRP happened, nitroglycerin (200 &micro;g) was “bolus” injected firstly into IRA to exclude the spasm of epicardial artery and identify SRP as well as a baseline and self-control agent following PCI. Ten minutes later, 1000 &micro;g of anisodamine was injected into IRA with SRP at 200 &micro;g/s, while the coronary angiography (CAG) was taken before and at 1st, 3rd and 10th minute after administration of nitroglycerin or anisodamine, respectively. The corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG) and the diameter of IRA were calculated and analyzed by Gibson’s TIMI frame count method using quantitative computer angiography (QCA) system to evaluate the influence of anisodamine on coronary flow and vessel lumen. In the meantime the invasive hemodynamic parameters of intracoronary and systemic artery (systolic, diastolic and mean pressure) and electrocardiogram (ECG) were measured and monitored. The changes of ventricular performance parameters and the adverse reaction were evaluated and followed-up at 1 month post-PCI. Results No significant changes in cTFCs and TMPGs were found at 1st, 3rd and 10th minute after intracoronary administration of nitroglycerin as compared with the baseline control (P＞0.05). cTFCs were decreased by 58.3%, 56.2%, and 54.6%, respectively (P&lt;0.001), and TMPGs were increased from 1.13±0.21 grade to 2.03±0.32, 2.65±0.45 and 2.51±0.57 grades (P&lt;0.05) at 1st, 3rd and 10th minute after intracoronary administration of anisodamine as compared with those after intracoronary administration of nitroglycerine, respectively. The average coronary blood flow of TIMI grade was improved from 1.76±0.43 to 2.71±0.46 (P&lt;0.05) while the diameter of middle segment in re-patented coronary artery was slightly increased from (3.20±0.40) mm to (3.40±0.50) mm at the 3rd minute after intracoronary administration of anisodamine (P＞0.05) as compared with those of nitroglycerine control. The systolic, diastolic and mean pressures of intracoronary artery after intracoronary administration of anisodamine increased from 115 to 123, 75 to 84, 88 to 95 mmHg (P&lt;0.05), respectively, along with the rise of heart rate from 68 to 84 beats per minute (P&lt;0.05). There were no significant changes in intervals of PR, QT and QRS (P＞0.05) and no any severe fast arrhythmia after intracoronary administration of anisodamine. The ventricular performance parameters were significantly improved and no major adverse cardiovascular events (MACE) were found during follow-up at 1 month post-PCI. Conclusions Intracoronary administration of 1000 &micro;g anisodamine is effictive in reversing SRP following PCI in STEAMI patients, especially it is suitable for SRP patients with bradycardia or hypotension.     

2%山莨菪碱霜预防5-氟尿嘧啶致化疗性静脉炎的效果评价

目的 探讨两种外用方法预防5-氟尿嘧啶(5-FU)所致化疗性静脉炎的临床效果.方法 选取广西医科大学第一附属医院2015年5月至2016年7月收治的80例采用顺铂+5-FU(PF方案)的化疗患者,根据入院时间分为观察组与对照组,各40例.外周静脉留置针穿刺成功后观察组沿穿刺静脉走向涂抹2%山莨菪碱霜自制制剂,对照组涂抹多磺酸黏多糖乳膏,比较两组干预后静脉炎发生情况和局部疼痛程度,以及干预前后两组血生化指标及炎性因子水平.结果 干预后,两组静脉炎等级分布及局部疼痛程度分布比较,差异均有统计学意义(Z=2.57、2.53,均P=0.01),观察组在减轻静脉炎损伤程度及缓解局部疼痛方面均优于对照组;干预前后比较,观察组白细胞(WBC)计数、平均血小板体积(MPV)及血小板体积分布宽度(PDW),对照组WBC、血小板(PLT)计数及血小板压积(PCT)差异均有统计学意义(P<0.05);两组患者PLT计数与PCT呈正相关(r=0.952,P<0.05);干预后两组高敏C反应蛋白(hs-CRP)水平及WBC计数比较,差异均无统计学意义(P>0.05).结论 2%山莨菪碱能有效预防和减轻5-FU所致化疗性静脉炎的发生和局部疼痛,同时PLT可以为预防化疗性静脉炎提供依据.     

抗胆碱药联合益血生治疗病窦综合征疗效观察

目的评估抗胆碱药并益血生对病窦综合征病人的用药及疗效.方法全部病例经EKG、DCE、阿托品试验,部分经食道心房调搏等多项检查确诊.观察组34例口服阿托品及益血生胶囊,依用药方式不同又分为A、B、C组.结果观察组显效率为35.3%,对照组为29.0%;观察组总有效率为79.5%,对照组为64.5%(P＜0.05),其中观察组中B组、C组的总有效率较高,与对照组比较有统计学意义(P＜0.01).结论抗胆碱药山莨菪碱(654-2)与益血生联合治疗病窦综合征疗效确切、安全,不良反应少.     

金锁固精丸加味联合654-2穴位注射治疗遗精40例临床观察

目的 观察金锁固精丸加味联合山莨菪碱(654-2)穴位注射治疗遗精的临床疗效.方法 选取遗精患者80例,随机分为观察组、对照组,各40例.观察组口服金锁固精丸加味联合654-2穴位注射,对照组给予舒乐安定片和谷维素片口服,观察对比两组的临床疗效.结果 观察组总有效率为90.0％,对照组总有效率为72.5％,两组对比差异有统计学意义(P＜0.05).结论 金锁固精丸加味口服联合654-2穴位注射治疗遗精疗效显著,值得临床推广.     

过度训练致大鼠心肌和肾组织细胞凋亡及山莨菪碱干预的影响

目的 同步研究过度训练致心肌和肾组织细胞凋亡及山莨菪碱干预的影响.方法 采用大鼠游泳至力竭方式建立过度训练模型,将大鼠随机分为对照组、力竭组及山莨菪碱组,力竭组又根据力竭后恢复时间分为力竭即刻组、力竭后6h组和力竭后24h组;山莨菪碱组于力竭运动前腹腔注射山莨菪碱10mg/kg,分为山莨菪碱干预后6h组和山莨菪碱干预后24h组.用TUNEL法、图像分析仪及流式细胞术检测各组大鼠心肌和肾组织细胞凋亡情况.结果 力竭即刻组大鼠心肌细胞凋亡较对照组增多(P＜0.05),力竭后6h组心肌细胞凋亡更为明显(P＜0.05),力竭后24h组心肌细胞凋亡明显减少,但仍明显高于对照组(P＜0.05);力竭即刻、6h、24h组大鼠肾组织细胞凋亡逐渐增多,与对照组比较,差异显著(P＜0.05).山莨菪碱干预后6h组和山莨菪碱干预后24h组心肌和肾组织凋亡细胞数较力竭同时间组明显减少(P＜0.05).结论 心肌和肾组织细胞凋亡是过度训练致心肌和肾脏损伤的细胞学基础;心肌损伤比肾损伤恢复快;山莨菪碱可通过抑制心肌和肾组织细胞的过度凋亡,对心、肾损伤起到明显的防治作用.     

山莨菪碱及其大鼠肠内菌体外代谢物的液相色谱-质谱法分析

目的 用液相色谱-电喷雾离子阱串联质谱联用法研究山莨菪碱在大鼠肠内菌中的代谢.方法 以山莨菪碱优化色谱及质谱条件,总结其色谱及质谱行为规律.将山莨菪碱与大鼠肠内菌体外厌氧温孵培养,并与空白样品及山莨菪碱对照品进行比较,依据被测物的多级质谱数据,鉴定代谢物并阐述其结构.结果 在温孵液中发现了山莨菪碱的脱水及水解代谢产物,即脱水山莨菪碱、6β-羟基托品和托品酸.结论 该方法灵敏、快速、简单,适合于药物代谢分析.     

山莨菪碱对耳蜗辐射防护作用的动物实验研究

目的研究山莨菪碱对耳蜗辐射损伤的防护作用。方法健康豚鼠25只随机分成三组：对照组、单纯放射组和山莨菪碱防护组,每组观察10耳。放疗前30分钟,按每公斤体重20mg于山莨菪碱防护组豚鼠的股部肌肉注射山莨菪碱,对照组和单放组在上述部位注射等量生理盐水。用直线加速器所产生的6Mev电子线对山莨菪碱防护组和单纯放射组豚鼠的耳颞部予以分次照射,总剂量达到60Gy后作耳蜗毛细胞的光镜及扫描电镜观察。结果耳蜗基底膜铺片表明对照组照射耳耳蜗内外毛细胞排列整齐无缺如,单纯放疗组照射耳耳蜗外毛细胞有大量缺如,内毛细胞有少许缺如,山莨菪碱防护组照射耳耳蜗外毛细胞少许缺如,内毛细胞无缺如;扫描电镜表明对照组照射耳耳蜗外毛细胞的纤毛排列整齐无倒伏、缺失,单纯放疗组照射耳耳蜗外毛细胞的纤毛明显倒伏、缺失、排列紊乱,山莨菪碱防护组照射耳耳蜗外毛细胞的纤毛排列基本整齐,偶见倒伏现象。结论①分割剂量60Gy对豚鼠耳颞部照射可造成耳蜗毛细胞损害,②山莨菪碱对耳蜗辐射损伤具有保护作用。     

The oxygen radical generator pyrogallol impairs cardiomyocyte contractile function via a superoxide and p38 MAP kinase-dependent pathway

Oxygen-derived free radicals have been demonstrated to contribute to the pathogenesis of myocardial dysfunction, although the underlying mechanism remains not fully understood. This study was designed to examine the role of the superoxide generator pyrogallol on cardiac contractile function and possible intervention with herbal medicines anisodamine and tetramethylpyrazine (TMP) on pyrogallol-induced cardiac contractile response. Adult rat ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an lonOptix system including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR₉₀), and maximal velocity of shortening/relengthening (±dL/dt). A 10-min exposure of pyrogallol (0 to 10⁻² M) did not affect cardiac contractile mechanics. However, longer duration of pyrogallol exposure (1, 3, and 6 h) significantly shortened resting cell length, reduced PS and ±dL/dt, and prolonged TPS and TR₉₀ in time- and concentration-dependent manners. The pyrogallol (10⁻⁴ M with 6-h incubation)-induced mechanical defects were prevented by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 (1 μM) and superoxide dismutase (SOD, 500 U/mL) with the exception that pyrogallol-induced PS depression was unaffected by SOD. Interestingly, incubation of herbal antioxidants anisodamine (10⁻⁷ M) and TMP (10⁻⁷ M) effectively attenuated the pyrogallol-induced cardiac mechanical defects with the exception of PS unaffected by TMP. Our data demonstrate a direct inhibitory effect of pyrogallol on cardiac contraction, probably in a superoxide- and p38 MAP kinase-dependent manner. The antioxidant medicines anisodamine and TMP may be useful in the treatment of oxygen free radical-induced myocardial dysfunction.