右美托咪定器官保护作用研究进展

右美托咪定是一种新型高选择性a₂肾上腺素能受体激动剂,广泛应用于重症医学科镇静,也广泛应用于围术期镇静镇痛,不仅有镇静镇痛作用,其在炎症抑制、免疫调节、器官保护作用方面也显示出明显的优势,笔者就右美托咪定最近几年的的文献,对其器官保护作用方面作一综述。     

右美托咪定用于食管癌手术安全性研究

目的观察右美托咪定用于食管癌患者全麻术后苏醒期及恢复期的影响。方法行开胸食管癌根治术患者90例,随机分为A组、B1和B2组,每组30例。在手术开始时A组泵注0.9%氯化钠溶液,而B1组泵注0.5μg/kg,15 min泵注完毕,而B2组泵注0.5μg/kg,15 min泵注完毕后以0.2μg·kg-1·h-1的剂量维持,记录3组患者入室时(T0)、拔管时(T1)、拔管后5 min(T2)、10 min(T3)、20 min(T4)、30 min(T5)的血压、心率、血氧饱和度、呼气末CO2分压等生命体征。记录3组患者拔管后苏醒时间,对苏醒期患者进行Ramsay镇静评分、躁动评分。对所有患者术后3 d行常规CT检查,对吸入性肺炎发病率进行分析。结果 A组内T0~T5各时间点HR、BP差异有统计学意义(P<0.05);而Sp O2和PCO2组间比较差异无统计学意义(P>0.05)。B1和B2组内T0-T5各时间点HR、BP、Sp O2和PCO2差异均无统计学意义(P>0.05)。而按T0~T5不同时间点内A、B1、B2组各指标比较,T2~T5的HR、BP在A组与B1、B2组间比较差异有统计学意义(P<0.05),但B1与B2组间各指标差异均无统计学意义(P>0.05)。B2组苏醒时间最长,其与A、B1组间比较差异有统计学意义(P<0.05),而A组与B1组间比较差异无统计学意义(P>0.05);镇静评分和躁动评分A组分别为最低和最高,A组与B1、B2组间比较差异有统计学意义(P<0.05),而B1和B2组间比较差异无统计学意义(P>0.05)。A组术后吸入性肺炎发病率最高,达16.6%,其与B1、B2组间差异有统计学意义(P<0.05),而B1与B2组间比较差异无统计学意义(P>0.05)。结论右美托咪定具有镇静、稳定血流动力学、抑制应激反应等优点,能明确降低开胸食管癌患者术后并发症发生,大大提高手术安全性,且不会延长患者苏醒时间,值得在临床广泛推广。     

右美托咪定诱导睡眠治疗顽固性失眠的疗效

目的观察右美托咪定诱导睡眠治疗顽固性失眠的临床效果。方法 60例顽固性失眠患者随机分为观察组和对照组,每组30例。对照组患者按《中国成人失眠诊断与治疗指南》给予治疗;观察组加用右美托咪定诱导睡眠。其方法是每晚22∶00静脉泵注右美托咪定0.6μg·kg^-1·h^-1,10 min后调整速率为0.25μg·kg^-1·h^-1维持50 min,共治疗7 d。记录两组治疗前和治疗结束时的匹兹堡睡眠质量指数(PSQI)评分和汉密尔顿焦虑量表(HAMA)评分。同时检测两组治疗前和治疗结束时的血清皮质醇水平,记录不良反应。结果治疗后,观察组PSQI总分低于对照组[(11.9±3.1)分vs.(15.1±2.9)分](P<0.05)。观察组和对照组治疗结束时的HAMA评分均低于治疗前[(8.9±1.4)分vs.(12.5±2.5)分]和[(10.3±2.1)分vs.(12.1±2.2)分](P<0.05),且治疗结束时观察组低于对照组(P<0.05)。观察组治疗结束时的血清皮质醇水平低于对照组[(2...     

右美托咪定的临床应用进展

右美托咪定（DEX）属于α2肾上腺素能受体的新型激动剂,具有高度的特异性。既能兴奋迷走神经,又能抑制交感神经,故临床多用于高血压、心动过速、心肌耗氧量增大、焦虑、疼痛及烦躁失眠等的治疗。2009年6月右美托咪定在我国上市,由于其独特的药理学特性,已在临床实践中显示出一定的优越性和应用价值,越来越受到麻醉医师的青睐。     

右美托咪定在甲状腺手术中的应用

目的观察右美托咪定在甲状腺手术中的有效性。方法选择择期颈丛麻醉下甲状腺手术40例,ASAⅠ或Ⅱ级,随机分为右美托咪定组(A组)和生理盐水对照组(B组)。记录麻醉前、诱导后、气管插管后、拔管后即刻收缩压、舒张压、心率变化。结果两组年龄、体重手术、时间均无统计学意义。两组患者麻醉诱导后心率、血压均明显下降(P<0.05或P<0.01),其中心率、收缩压A组明显低于B组(P<0.05);气管插管后、拔除气管导管后即刻,心率、收缩压、舒张压A组明显低于B组(P<0.05)。结论颈丛神经阻滞常引起血压升高,心率加快,右美托咪定具有镇静、镇痛和抗交感作用,在颈丛麻醉的甲状腺手术中使血压和心率平稳,并减少麻醉镇痛和药用量。     

右美托咪定的临床麻醉应用研究进展

临床中,最为常用的药物是右美托咪定,其能够起到镇痛、镇静的效果,同时对于呼吸的抑制比较低,因此在临床麻醉和手术麻醉中比较常用。其不仅能够降低镇静药物的使用量,在很大程度上也能够降低不良反应的发生率。本次就临床中应用右美托咪定情况进行研究。     

右美托咪定用于临床镇静的研究进展

右美托咪定是一种对α2肾上腺素受体具有高选择性的激动剂,不但有剂量依赖性的镇静作用,同时还具有镇痛、抗交感、抗焦虑、抑制应激反应、减少麻醉药物的用量以及使血液动力学趋于稳定等生理活性,目前已成功应用于麻醉术前用药、全身麻醉时辅助用药、神经外科手术及术后镇静镇痛等临床实践中。该文对右美托咪定的药理学性质及其在镇静中的应用进展进行了介绍。     

右美托咪定肺保护作用的研究进展

在目前,右美托咪定（dexmedetomidine, DEX）是一种高选择性的α2肾上腺素能受体（α2-adrenergic receptor,α2-AR）激动剂,具有中枢性抗交感作用,能产生近似自然睡眠的镇静作用;同时具有一定的镇痛、利尿和抗焦虑作用,对呼吸无抑制,在临床麻醉镇静中得到了广泛的应用。随着临床研究深入,发现其对人体脑部、心肌组织、肾脏、肝脏以及肺脏等具有显著的保护作用,现对其在肺保护及作用机制的研究进展予以综述。     

右美托咪定在颅内动脉瘤栓塞术中的应用

<正>颅内动脉瘤破裂在DSA全麻下行动脉瘤栓塞术,要求患者在麻醉诱导插管及拔管过程中血流动力学平稳,术后苏醒迅速,避免因患者呛咳躁动引起血压过渡波动而诱发动脉瘤再次破裂出血。而患者在全麻诱导插管特别是拔管过程中发生呛咳,躁动的概率非常高,从而血压的波动很大,增加了患者术后脑出血脑水肿脑疝的风险。本文应用     

右美托咪定治疗快速性室上性心律失常1例

右美托咪定是一种新型镇静剂,它是α2肾上腺素能受体激动剂,右美托咪定具有良好镇静镇痛效果,同时无呼吸抑制,还具有抗焦虑、减少寒战反反应、减轻炎性反应以及心脏、肾脏、神经等保护作用,目前主要用于麻醉过程及ICU中镇静治疗。其主要不良反应为低血压及心动过缓,最近利用右美托咪定对心血管系统的负性变时及变传导作用,作为治疗快速性室上性心律失常的一种治疗方法 ,在儿童先天性心脏病患者围手术期发生的快速性室上性心律失常治疗中取     

Separate effects of cigarette smoke yield and smoke taste on smoking behavior

The purpose of this experiment was to compare independently the influence of different cigarette smoke taste categories and different machine standard smoke yield values on cigarette smoking behavior and related subjective measures. In six separate sessions 15 regular smokers were presented with a medium and a low smoke yield cigarette of each of the three taste categories, mentholated, dark (Gauloises) and blond (Muratti) tobacco. Each session, included a natural and a forced smoking procedure of one cigarette type only. Forced smoking consisted of smoking 30 puffs whereby a new half-length cigarette was presented after every third puff. During the seventh session, habitual brand cigarettes were smoked as a reference. The sessions followed in weekly intervals, and the subjects became familiar with the test cigarettes during the last 5 days preceding each test session. Although general acceptability of the cigarettes, smoking satisfaction and pleasantness of taste were clearly lower for all test cigarettes as opposed to the habitual brand reference, cigarettes, these measures remained unaffected by taste or smoke yield of the test cigarettes. Harshness of smoke was higher in the dark tobacco category and generally decreased with the lower smoke yield cigarettes. Independent effects of taste and smoke yield were obtained for total puff volume, inhalation time and CO absorption, suggesting a compensatory intensification of smoking behavior for low yield cigarettes and an independent increase of smoking intensity from mentholated to dark tobacco to blond tobacco. The results suggest therefore that factors which affect cigarette smoke taste have effects on smoking behavior which are separate from those obtained by comparing smoke yields.     

Hydroxychloroquine attenuates cigarette smoke induced autophagic signaling in the mouse ovary

We previously demonstrated that Cigarette Smoke (CS) induces autophagy in the ovary. Therefore we aimed to determine if chloroquine (CQ) could inhibit CS-induced autophagy in the ovary. Eight week old mice were implanted with CQ pellets; 0, 25, and 50 mg CQ/kg. Half of the animals in each group were exposed to room air and the other half were exposed to CS twice daily for 8 weeks. Ovaries were harvested for electron microscopy, gene and protein expression analysis. There was a significant increase in the production of autophagosomes in granulosa cells of mice exposed to CS (p = 0.0297). However 25 and 50 mg/kg CQ treatment significantly decreased the CS-induced autophagosomes (p = 0.0505; p = 0.0065) and attenuated the effects of CS on LC3B and BECN1 expression. In summary, this suggests that CQ attenuates CS-induced autophagy in the ovary and that ovarian protection from toxic insult is potentially feasible.     

芹菜素对烟草烟雾提取物诱导血管内皮细胞损伤的作用

目的探讨芹菜素改善烟草烟雾提取物诱导的血管内皮细胞损伤的机制。方法培养人脐静脉内皮细胞株,给予烟雾提取物(CSE)模拟吸烟环境和不同浓度芹菜素。实验分为正常对照组、CSE组、芹菜素组,检测细胞存活率、凋亡率、细胞内活性氧ROS水平,以及细胞上清液中IL-6、TGF-β、INF-γ各因子的表达。结果芹菜素在24 h和48 h均能显著缓解不同浓度CSE诱导的内皮细胞存活率的降低,降低不同浓度CSE诱导的内皮细胞的凋亡率,同时芹菜素可抑制CSE诱导的细胞内ROS水平,以及上清液中炎性因子IL-6、TGF-β、INF-γ的升高,差异均有统计学意义(P<0.05,P<0.01)。结论芹菜素以血管内皮细胞凋亡和炎性反应为标靶,抑制吸烟引起的血管内皮细胞损伤,为临床治疗提供理论依据。     

Cyclooxygenase-2 in cancer cells and macrophages induces colon cancer cell growth by cigarette smoke extract

Cigarette smoking, cyclooxygenase-2 (COX-2) and macrophages are independently associated with colorectal cancer. In the present study, cigarette smoke ethanol extract was applied to colon cancer cells (SW1116) or indirectly via activated macrophages (THP-1 cells) to attest their effects on cancer cell proliferation and tumor growth both in vitro and in vivo. Ethanol extract induced COX-2 expression in SW1116 and THP-1 cells. Combination of THP-1 pre-incubated medium and ethanol extract further potentiated COX-2 expression and proliferation of SW1116 cells. Tumor growth in nude mice was positively associated with the medium and/or ethanol extract treatments, together with the up-regulation of cell proliferation and angiogenesis, and down-regulation of apoptosis. Application of a COX-2 inhibitor (SC236) reduced tumor growth as well as cell proliferation and angiogenesis. These actions are partially depended on the decrease of COX-2 expression. Taken together, inhibition of COX-2 activity may have significant implication to prevent colon cancer in smokers.     

Inhibitory effects of cigarette smoke extracts on neural differentiation of mouse embryonic stem cells

Maternal smoking during the perinatal period is linked to adverse neonatal outcomes such as low birth weight and birth defects. Numerous studies have shown that cigarette smoke or nicotine exposure has a widespread effect on fetal nerve development. However, there exists a lack of understanding of what specific changes occur at the cellular level on persistent exposure to cigarette smoke during the differentiation of embryonic stem cells (ESCs) into neural cells. We previously investigated the effects of cigarette smoke extract (CSE) and its major component, nicotine, on the neural differentiation of mouse embryonic stem cells (mESCs). Differentiation of mESCs into neural progenitor cells (NPCs) or neural crest cells (NCCs) was induced with chemically defined media, and the cells were continuously exposed to CSE or nicotine during neural differentiation and development. Disturbed balance of the pluripotency state was observed in the NPCs, with consequent inhibition of neurite outgrowth and glial fibrillary acidic protein (Gfap) expression. These inhibitions correlated with the altered expression of proteins involved in the Notch-1 signaling pathways. The migration ability of NCCs was significantly decreased by CSE or nicotine exposure, which was associated with reduced protein expression of migration-related proteins. Taken together, we concluded that CSE and nicotine inhibit differentiation of mESCs into NPCs or NCCs, and may disrupt functional development of neural cells. These results imply that cigarette smoking during the perinatal period potentially inhibits neural differentiation and development of ESCs cells, leading to neonatal abnormal brain development and behavioral abnormalities.     

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.     

Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

Aims

Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved.

Methods

CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca²⁺]_i was measured by flow cytometry using fluo-3. Mitochondrial [Ca²⁺] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy.

Results

CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca²⁺ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca²⁺]_i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca²⁺]_i during P-MI was also prevented by ranolazine.

Conclusions

CSE in clinically relevant concentrations increases myocyte [Ca²⁺]_i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold.     

Induction of nitroarenes in cigarette smoke condensate treated with nitrate

Samples of cigarette smoke condensates (CSCs) treated with nitric acid or Chinese cabbage pickles having a high nitrate content strongly mutated Salmonella typhimurium strain TA98; the benzene/ethanol extract after these treatments induced 1800 and 820 revertants, respectively, per mg of extract for strain TA98 in the absence of S9 mix. The major mutagens in these materials were found to be 1-nitropyrene and 1,3-dinitropyrene on the basis of the result of gas chromatography/mass spectrometry and of fluorescence spectra of the samples. The quantity of 1-nitropyrene was 14.5 ng per cigarette for the CSCs treated with nitric acid, and for 11.2 ng for those treated with Chinese cabbage pickles. Similarly, 1,3-dinitropyrene was detected in the CSCs treated with nitric acid or Chinese cabbage pickles at concentrations of 0.38 and ˜0.1 ng, respectively, per cigarette.     

Apoptotic effects of cigarette smoke extracts on mouse embryonic stem cells via oxidative stress

Previous studies have reported that cigarette smoke and cigarette smoke extract (CSE) have negative effects on embryonic development. However, no studies have investigated the mechanism through which CSE affects the cellular signaling pathway leading to apoptosis and oxidative stress in embryonic cells, or how the two pathways are cross‐linked. Thus, we studied the effects of CSE on apoptosis and oxidative stress in mouse embryonic stem cells (mESCs). Specifically, we measured changes in cell viability in response to CSEs (3R4F and two domestic cigarettes CSE 1 and 2) using a water soluble tetrazolium (WST) assay and a neutral red uptake (NRU) assay, which revealed that cell viability decreased in a concentration‐dependent manner. Western blot analysis revealed that the expression of cyclin D1 and cyclin E1 was decreased and that of p21 and p27 was increased by CSE. Additionally, the number of terminal deoxynucleotidyl transferase (TUNEL)‐stained cells was increased by CSE, while the levels of Bax and Caspase‐3 increased and Bcl‐2 decreased. Moreover, a 2′,7′‐dichlorofluorescin diacetate (DCF‐DA) assay and reactive oxygen species (ROS)‐Glo H₂O₂ assay confirmed that ROS were generated in response to CSE and that they were associated with up‐regulated Keaf‐1 and CHOP. Overall, the results revealed that cigarette smoke extract (CSE) inhibited cell proliferation by regulating cell cycle‐related protein expression and increased oxidative stress by regulating the expression of Kelch‐like ECH‐associated protein 1 (Keap‐1) and CCAAT/enhancer‐binding protein homologous protein (CHOP), resulting in apoptosis in mESCs.