壳聚糖微球的纤毛毒性和黏附力的考察

目的:考察鼻黏膜用壳聚糖微球的纤毛毒性及黏附力.方法:采用在体蟾蜍上腭纤毛试验法,通过测定纤毛摆动持续时间评价微球制剂的鼻纤毛毒性,测定纤毛输送速率评价微球的黏膜黏附力.结果:壳聚糖微球能显著地降低鼻纤毛毒性,并且具有良好的生物黏附性.结论:壳聚糖是理想的鼻腔给药系统的载体材料.     

薄荷脑鼻腔原位凝胶剂的制备及安全性研究

目的 制备薄荷脑鼻用原位凝胶剂,并对其进行安全性考察。方法 采用去乙酰结冷胶为材料制备离子敏感性原位凝胶。考察鼻腔原位凝胶对蟾蜍鼻黏膜纤毛的毒性及大鼠鼻黏膜的影响;并进行家兔皮肤刺激实验和豚鼠皮肤过敏实验,观察皮肤反应并评分。结果 薄荷脑鼻用原位凝胶剂对蟾蜍鼻黏膜纤毛无显著毒性,对大鼠鼻黏膜形态及细胞分化无显著影响;对家兔完整皮肤无刺激作用,豚鼠皮肤无过敏反应。结论 薄荷脑鼻用原位凝胶剂具有制备工艺简便、纤毛毒性低、生理相容性好的优点,开发为经鼻给药系统可行性良好。     

功能性鼻内镜术后鼻黏膜变化及其临床意义

目的:观察功能性鼻内镜术(FESS)后鼻黏膜变化,为完善治疗、提高手术治愈率提供科学的依据。方法:采用M esserk linger术式治疗慢性鼻窦炎、鼻息肉患者83例,分别于FESS术后1个月和4个月取其前筛区黏膜标本;以鼻中隔偏曲患者(既往无鼻窦炎病史)作为对照,光镜观察以及检测鼻黏膜纤毛清除速率(MTR)。结果:光镜观察:FESS术后1个月前筛区黏膜上皮有67例为鳞-柱交界上皮,16例为假复层柱状纤毛上皮;术后4个月前筛区黏膜83例基本恢复为假复层柱状纤毛上皮。鼻黏膜纤毛清除速率:FESS术后1个月与4个月比较、FESS术后1个月与正常对照组比较M TR之间差异均有显著性(P<0.05),FESS术后4个月与正常对照组间无显著差异。结论:鼻内镜术后鼻黏膜可以再生,术后4个月黏膜基本恢复为假复层柱状纤毛上皮;术后4个月M TR恢复正常。     

通窍汤对家兔实验性鼻窦炎鼻黏液纤毛输送功能的影响

目的探讨通窍汤对家兔实验性急性化脓性鼻窦炎鼻黏液纤毛输送功能的影响。方法采用改良后的Hinni造模法建立实验性急性化脓性鼻窦炎模型。予以通窍汤高、低剂量灌胃治疗,并设立空白组、模型组、西药（青霉素V钾灌胃）组作为对照。观察通窍汤对实验性急性化脓性鼻窦炎家兔鼻黏膜纤毛传输时间、光镜观察窦腔黏膜炎症情况、扫描电镜下观察窦腔黏膜纤毛上皮纤毛的变化情况。结果实验性急性化脓性鼻窦炎家兔鼻黏膜纤毛传输时间延长、光镜、电镜下窦腔黏膜充血、水肿、纤毛脱落等。通窍汤低剂量治疗后,鼻窦炎家兔鼻黏膜纤毛传输时间缩短,光镜、扫描电镜下窦腔黏膜正常等。青霉素V钾和通窍汤高剂量治疗后,上述病理改变有明显改善,但与通窍汤低剂量相比,稍有差异。结论通窍汤可消除急性化脓性鼻窦炎家兔局部的炎症反应,加快鼻窦黏液纤毛传输时间。     

抗动脉粥样硬化基因疫苗经鼻腔免疫黏膜毒性的初步评价

目的:考察抗动脉粥样硬化基因疫苗经鼻腔接种免疫的黏膜毒性.方法:以壳聚糖为基因载体,制备载基因疫苗的壳聚糖纳米粒.对高脂家兔模型滴鼻免疫6次,28周时取鼻黏膜及肺部组织行组织病理学检查,扫描电镜观察鼻黏膜纤毛的超微结构变化.结果:基因疫苗经鼻腔免疫可以显著诱导抗体,延缓动脉粥样硬化的发展.组织病理学检查表明,鼻黏膜及肺部组织形态正常.黏膜纤毛超微结构的扫描电镜观察表明,鼻黏膜纤毛排列有序,无断裂、脱落、倒伏等异常现象.结论:基因疫苗经鼻腔接种未致黏膜及纤毛损伤,鼻腔给药有潜力发展为一种新的接种途径.     

鼻内镜下改良型鼻中隔成形术的临床观察

目的探讨鼻内镜下改良型鼻中隔成形术治疗鼻中隔偏曲及单侧前鼻孔狭窄的效果。方法对58例鼻中隔偏曲及7例伴单侧鼻瓣狭窄的患者行鼻内镜下鼻中隔改良三线减张结合鼻中隔软骨碎片化处理的诊治过程行回顾性分析,进行术前、术后3个月鼻塞视觉模拟量评分(VAS)、总鼻阻力测定、鼻黏膜纤毛输送率的检查。结果所有患者行鼻内镜下改良型鼻中隔成形术后鼻塞、头痛、鼻出血等不适症状均得到有效改善,术后3个月平均VAS评分(2.52±0.55)分及平均鼻阻力(0.28±0.06)kPa/(L·s)较术前明显下降,差异具有统计学意义(P<0.05),但平均鼻黏膜纤毛输送率(6.54±1.23)mm/min无明显变化,差异无统计学意义(P>0.05),随诊6个月以上,未出现鼻中隔穿孔、鼻中隔摆动、鼻梁塌陷及鼻中隔再发偏曲等并发症。结论鼻内镜下改良型鼻中隔成形术,术野清晰,能有效改善鼻腔通气功能,在有效矫正鼻中隔偏曲的基础上最大限度保留了鼻中隔支架,降低了鼻中隔穿孔、鼻中隔摆动及鼻梁塌陷的风险。     

复方双辛喷雾剂的纤毛毒性作用及黏膜刺激性实验研究

目的考察复方双辛喷雾剂对蛙口腔黏膜纤毛的影响及对大鼠鼻腔黏膜的刺激性。方法在光学微镜下观察离体蛙口腔上腭纤毛在药物溶液作用下的持续摆动时间，以此为指标考察复方双辛喷雾剂的纤毛毒性大小；对大鼠连续给予复方双辛喷雾剂1周，取鼻黏膜作组织切片检查，观察黏膜有无病理变化。结果复方双辛喷雾剂对纤毛运动影响较小，与药物对照组相比，P〈0．05；组织切片显示黏膜也无显著病理改变。结论复方双辛喷雾剂对蛙口腔纤毛的功能无明显损伤作用，常规剂量对大鼠鼻黏膜也无明显刺激性。     

富马酸比索洛尔鼻喷剂对蟾蜍上颚纤毛运动的影响

目的 考察富马酸比索洛尔鼻喷剂及其附加剂对蟾蜍上颚纤毛运动的影响。方法 以生理盐水作为对照,10 mg/mL去氧胆酸钠溶液作为阳性对照,比较100 μL富马酸比索洛尔鼻喷剂、25 mg/mL富马酸比索洛尔溶液、5 mg/mL三氯叔丁醇溶液以及30 mg/mL 2,6-二甲基-β-环糊精(2,6-DM-β-CD)溶液对离体、在体蟾蜍上颚黏膜纤毛持续运动时间(LTCM),并观察组织形态的变化。结果 离体实验中对照组测得的LTCM为最大值,黏膜表面和纤毛清晰完整,纤毛运动活跃。25 mg/mL富马酸比索洛尔溶液、5 mg/mL三氯叔丁醇溶液和30 mg/mL 2,6-DM-β-CD溶液组黏膜纤毛持续摆动30～50 min后,以生理盐水冲洗后,则又很快恢复摆动,而且持续时间很长,且黏膜表面完整,未见纤毛脱落现象。在体实验中对照组黏膜表面完整,纤毛运动非常活跃,测得其LTCM为300 min,富马酸比索洛尔鼻喷剂组与对照组比较,差异无显著性。结论 富马酸比索洛尔鼻喷剂及其附加剂经鼻腔给药后对鼻黏膜纤毛的毒性较小且为短暂和可逆的,为今后研究该药物的鼻腔给药新制剂提供了重要参考。     

鼻窦炎口服液鼻腔冲洗对鼻黏膜纤毛系统功能的影响

目的:观察鼻内镜术后应用鼻窦炎口服液鼻腔冲洗对鼻黏膜纤毛运输功能的影响。方法:对接受鼻内镜术患者,术后用不同冲洗液鼻腔冲洗,测定术前、术后3mo黏膜纤毛运输功能。结果:术后应用鼻窦炎口服液冲洗鼻腔,3mo时黏膜纤毛运输功能基本恢复正常。结论:鼻内镜术后应用鼻窦炎口服液冲洗能促进窦口鼻道复合体黏膜纤毛功能的恢复。     

慢性鼻-鼻窦炎内镜手术前后OMC区分泌腺的观察研究

目的:观察慢性鼻窦炎(CS)鼻内镜鼻窦手术前后鼻黏膜黏液纤毛清除系统的分泌腺结构和功能变化。方法:对20例慢性鼻窦炎术前及术后4个月窦口鼻道复合体(OMC)区鼻黏膜进行AB-PAS染色,光镜下观察,并与健康组(对照组10例)进行对照。结果:鼻窦炎术前组黏膜怀状细胞及黏膜下腺体有显著性增加(P<0.01),型鼻窦炎患者病理性腺体的增生尤为明显。内镜术后4个月鼻黏膜杯状细胞可恢复至正常水平,与对照组比较差异无显著性(P>0.05),而黏膜下腺体未能恢复正常。结论:鼻黏膜杯状细胞及黏膜下腺体的增生是黏液纤毛清除功能障碍的原因之一,尤其是病理性腺体的增生。内镜术后4个月鼻黏膜上皮化,但黏液纤毛清除系统的恢复需要更长时间。术后随访时间应超过4个月,以防复发。     

An improved primary human nasal cell culture for the simultaneous determination of transepithelial transport and ciliary beat frequency

Objectives The aim was to establish a preclinical in‐vitro system of the nasal mucosa for the simultaneous evaluation of nasal absorption and effects on ciliary activity. Methods Human nasal epithelial cells were grown in collagen‐coated transport inserts with transparent polyethylene terephthalate membranes (3 μm). Transepithelial transport and ciliary beat frequency values were measured every 15 min for 1 h. Key findings The apparent permeability coefficients (P_app) for atenolol (mainly paracellular transport) and propranolol (transcellular transport) amounted to 0.1 ± 0.1 and 23.7 ± 0.6 × 10^?6 cm/s, respectively, illustrating that the system can be used to discriminate between high permeability and low permeability compounds. Transport of talinolol (substrate for the P‐glycoprotein efflux carrier) did not reveal polarity (0.3 ± 0.2 and 0.2 ± 0.1 × 10^?6 cm/s for absorptive and secretory transport, respectively) and was not affected by verapamil (10 μm), suggesting the absence of P‐glycoprotein in the nasal cell culture. No significant effects of atenolol, propranolol and talinolol on ciliary beat frequency were observed (98 ± 20% of the control condition after 60 min). Chlorocresol significantly decreased the ciliary activity but this decrease was not accompanied by effects on the transepithelial transport of atenolol, propranolol and talinolol. Conclusions A new system was developed which offers possibilities as a fast screening tool for studying the potential of compounds for nasal drug administration, since permeability and a possible cilio‐toxic effect can be assessed simultaneously.     

感染性休克患者早期血降钙素原及纤维蛋白原变化的临床意义

目的探讨感染性休克患者早期血降钙素原及纤维蛋白原的表达水平及其临床意义。方法选取于我院2013年1-12月收治40例感染性休克患者,同时选取同期于我院住院的40例非感染性休克者为对照组,分别于治疗前及治疗后第1、3、5天采取静脉血分别检测降钙素原、纤维蛋白原的变化。结果与对照组比较,感染性休克治疗前及治疗后第1、3、5天患者血降钙素原及纤维蛋白原水平明显升高（P〈0.05）,治疗后感染性休克组治疗后第1、3天逐渐升高,于治疗后第3天达到高峰后逐渐下降,治疗后第5天血降钙素原及纤维蛋白原水平明显低于第3天（P〈0.05）。结论早期联合监测血降钙素原及纤维蛋白原的变化有助于判断感染性休克患者病情严重程度。     

Effects of captopril (SQ 14, 225) on the renin-angiotensin-aldosterone system in normal rats

High doses of captopril (SQ 14, 225) (120-160 mg/kg/day) were administered orally to normal rats, and the effects on the renin-angiotensin-aldosterone system were observed. Plasma angiotensin converting enzyme (ACE) activity was elevated significantly on the 3rd, 7th and 30th days of captopril administration. ACE activity in the lung and the kidney was significantly decreased on the 1st day then gradually increased, becoming significantly higher than that of controls by the 30th day. Plasma renin activity (PRA) was significantly elevated on the 1st day and remained at a high level until the 30th day. Renal renin content was found to be significantly lower on the 1st and 3rd days. Plasma aldosterone concentration was not affected by captopril treatment, whereas serum potassium concentration was found to be significantly lower on the 1st, 3rd and 30th days. It is suggested that besides its inhibitory action on ACE, captopril has a direct or indirect stimulating action on ACE production as well as on renin release.     

盐酸氯胺酮喷雾剂经鼻黏膜吸收动力学及纤毛毒性研究

目的研究盐酸氯胺酮喷雾剂的经鼻黏膜吸收动力学以及纤毛毒性。方法测定家兔鼻黏膜蛤药后血药浓度,计算药动学参数;采用在体蛙上碍评价药物纤毛运动的影响。结果经鼻黏膜给药后,达峰时间Tmax为2．83min,峰浓度Cmax为69．07μg·mL^-1,MRT为44．59min,曲线下面积AUC为567．43μg·min·mL^-1,绝对生物利用度为42．29％;给予盐酸氯胺酮喷雾剂及空白基质后。纤毛运动持续时间分别为510±63min和562±51min。结论盐酸氯胺酮经鼻黏膜吸收动力学符合单室药动学模型,一级吸收动力学特性;给予盐酸氯胺酮喷雾剂及空白基质后。纤毛稍有杂乱。但纤毛运动较活跃．说明本制剂的纤毛毒性较小。     

微创鼻中隔矫正导尿管负压吸引不填塞鼻腔的临床应用

目的探讨鼻中隔矫正术后不填塞鼻腔的可行性。方法选择53例单纯鼻中隔偏曲患者,在鼻内镜下行鼻中隔矫正,对46例双侧黏骨膜无损伤或位于前部的能缝合小裂伤患者,术后不填塞鼻腔、术腔置导尿管持续负压吸引。结果46例患者中,术后3d出血量为（8．1±5．6）ml,33例术后3d的水肿程度较轻,下鼻甲与鼻中隔间距适中,鼻腔通气良好;其中13例术后24h鼻黏膜反应性水肿较重（5例为变应性鼻炎）,应用呋麻滴鼻液及激素喷鼻后鼻黏膜收缩敏感,通气良好,3d后拔管直到一期愈合。所有病例均达治愈,未发生鼻中隔血肿,随访半年以上,无并发症。结论鼻中隔矫正术后,只要双侧黏骨膜无裂伤,术腔置导尿管持续负压吸引,不填塞鼻腔是可行的。     

重症新冠肺炎患者经鼻高流量氧疗联合呼吸功能锻炼的护理

目的:探讨重症新冠肺炎患者经鼻高流量氧疗联合呼吸功能锻炼的护理经验。方法:对6例重症新冠肺炎患者实施经鼻高流量氧疗、加强呼吸功能锻炼、预防并发症、心理护理、三级防护,观察其效果。结果:4例患者在治疗7 d后氧合及呼吸状态明显改善,改为经双鼻塞进行序贯氧疗;1例患者在治疗7 d后氧合指标明显改善,但自觉症状改善不明显,加强心理护理同时改面罩序贯治疗;1例患者治疗中因氧合变差及症状加重,行气管插管及有创呼吸机辅助治疗。结论:经鼻高流量氧疗联合呼吸功能锻炼在新冠肺炎重症患者中值得推广。     

尼莫地平鼻用冻干脂质体的小鼠药效学及纤毛毒性

采用小鼠模型，验证尼莫地平脂质体鼻黏膜给药的药效学。结果表明，对小鼠抗脑缺氧、抗急性脑缺血及抗急性脑栓塞形成等均有显著的保护作用，其药效与腹腔注射尼莫地平溶液接近，显著优于灌胃给药。另采用蟾蜍上颚纤毛模型，考察了空白脂质体及含药脂质体的纤毛毒性，结果表明尼莫地平脂质体对纤毛运动和形态有一定影响。     

Effects of Viscous Hyaluronate–Sodium Solutions on the Nasal Absorption of Vasopressin and An Analogue

The effects of viscous solutions of hyaluronate-sodium of various average molecular weights (MW) on the nasal absorption of vasopressin (AVP) and its analogue, l-deamino-8-D-arginine vasopressin (l-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 × 10⁵ daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 × 10⁴ daltons were not effective. The enhancing effects on the nasal absorption of AVP and l-d-8-DAVP were dependent on the concentration in the range of 0–1.5% (w/v) hyaluronate (MW 1.4 × 10⁶ daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and l-d-8-DAVP in hyaluronate solutions (MW 1.4 × 10⁶ and 2 × 10⁶ daltons) increased more than 2- and 1.6-fold as compared to nasal administration of AVP and 1-d-8-DAVP in buffer solutions (pH 7.0), respectively. Hyaluronate solution (MW 1.4 × 10⁶ daltons) did not affect the ciliary beat frequency of rabbit nasal mucosal membranes in vitro. Therefore, hyaluronate solution may be useful as a vehicle for nasal delivery of AVP and l-d-8-DAVP.     

鼻腔用药治疗小儿普通感冒的临床观察

目的 :探讨鼻腔用药对小儿上呼吸道感染的疗效。方法 :对我院确诊为上感的门诊患儿 5 6 9例 ,用林可霉素眼液、可的松眼液、麻黄素滴鼻液配成混合液滴鼻 ,分别于治疗 3d、5d、7d后随访治疗效果。结果 :3d、5d、7d治愈率分别为 86 6 %、93 5 %、97 7%。婴儿组 36例 3d治愈率 94 4 4 %。结论 :用林可霉素眼液、可的松眼液、麻黄素滴鼻液配成混合液滴鼻治疗小儿上呼吸道感染有效 ,提示对预防婴幼儿中耳炎、鼻窦炎有重要临床意义     

甘辛喷雾剂的鼻黏膜纤毛毒性评价

目的:确定适宜的药物浓度,评价甘辛喷雾剂及处方各组分对鼻黏膜纤毛功能的影响.方法:用光学显微镜观察离体蛙口腔上腭纤毛在药物溶液作用下持续摆动时间,以此作为指标考查不同药物浓度和组分对蛙口腔黏膜纤毛功能的影响.结果:4%甘辛喷雾剂对纤毛运动影响最小,与对照组药物相比,4%甘辛喷雾剂和处方中各组分对蛙口腔黏膜纤毛的影响弱于滴通鼻炎水(P＜0.01).结论:甘辛喷雾剂对鼻黏膜纤毛的功能无明显损伤作用.