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双黄连粉针剂超声雾化吸入的安全性实验研究

The Experimental Study on the Safety of ShuangHuangLian Powder Injection Ultrasonic Atomization Inhaling

【作者】 唐昊

【导师】 杨仁旭;

【作者基本信息】 成都中医药大学 , 中医内科学, 2013, 博士

【摘要】 目的:通过对昆明种小鼠雾化吸入双黄连粉针剂溶液,光镜下观察各组小鼠肺部病理切片、测量各组小鼠体重、肺湿重,计算肺指数,检测小鼠肺组织中CC16的表达以及血清中Hyp、I1-8的含量,初步评估双黄连粉针剂雾化吸入的安全性。方法:取健康两周龄昆明种小鼠72只,随机分为空白组、对照组、地塞米松组(简称地米组,下同)、双黄连粉针低剂量组(简称低剂量组,下同)、中剂量组、高剂量组六组。空白组不予任何处理,对照组予蒸馏水进行雾化,地米组予地塞米松注射液进行雾化,其余组以不同浓度的双黄连粉针剂溶液(低、中、高剂量组)雾化吸入。30日后称取小鼠体重,处死后,称取小鼠肺湿重,计算出每只小鼠肺指数,并通过肺组织的病理切片了解气道结构等变化情况,采用免疫组织化学法检测各组小鼠肺组织中CC16含量,取血清用酶联免疫吸附法(ELISA法)测量HYP、IL-8含量。结果:病理切片提示:空白组、对照组、地塞米松组均有1只小鼠肺组织局灶性纤维组织增生,伴炎性细胞浸润;其余支气管管壁完整,管腔圆整,管壁和平滑肌厚度正常,血管腔、肺泡腔、肺间质未见炎性细胞的浸润。双黄连低剂量组:3只小鼠肺组织局灶性纤维组织增生伴炎性细胞浸润,其余未见明显异常。中剂量组:2只小鼠肺组织局灶性纤维组织增生伴炎性细胞浸润,其余未见异常。高剂量组:2只小鼠肺组织局灶性纤维组织增生伴炎性细胞浸润,其余未见明显异常。将各组小鼠病理切片分级、统计分析后,结果具有统计学意义(p<0.05)。实验指标方面,与对照组比较,地塞米松组小鼠体重、肺湿重,有统计学意义(p<0.05);与对照组比较,各组小鼠肺指数无统计学意义;与对照组比较,高剂量组、地塞米松组小鼠肺组织中CC16表达明显增高,有统计学意义(p<0.05);中剂量组、低剂量组、地塞米松组小鼠血清中Hyp含量明显增高,有统计学意义(p<0.05);中剂量组、低剂量组、地塞米松组小鼠血清中IL-8含量明显增高(p<0.05),有统计学意义。结论:在本实验中,双黄连粉针剂雾化吸入后,小鼠肺组织产生了一定的损伤,值得警醒,其具体损伤机制值得进一步研究。提示双黄连粉针剂、地塞米松等静脉注射用药不能随意用于雾化,临床医生一定要按照药品说明书的用药途径给药。

【Abstract】 Objective:Through atomizing ShuangHuangLian powder injection solution to the Kunming mice, observe each group of mice lung biopsy, the body weight of mice, lung wet weight, the lung index as well as the lung tissue of mice CC16expression and serum HypIL-8content. Make a preliminary assessment of the security of ShuangHuangLian powder injection inhalation.Methods:Take healthy72, only two weeks kunming mice were randomly divided into blank group, the control group, dexamethasone group, ShuangHuangLian booster injection of low dose group (referred to as the low dose group, similarly hereinafter), middle dose group, high dose group, six groups. Blank group will not be any processing, the control group in the distilled water atomization, the rest of the group with different concentrations of ShuangHuangLian powder injection solution (low, medium and high dose group) aerosol inhalation. After30days according to weight the mice, put to death, according to take in mice lung wet weight, calculate each mouse lung index. Observe the lung tissue pathological airway structural changes. Take immunohistochemistry to detect the group the CC16content in the lung tissue of mice, take serum enzyme linked immunosorbent assay method (ELISA) for measuring content of HYP, IL-8.Results:Biopsy Tip:blank control group, dexamethasone group were a focal proliferation of fibrous tissue of mouse lung tissue with inflammatory cell infiltration; complete the rest of the bronchial wall, lumen rounded wall and smooth musclenormal thickness, the quality no inflammatory cell infiltration in the vessel lumen, alveolar space, lung. The Shuanghuanglian low-dose group:three mouse lung tissue focal fibrous tissue hyperplasia with inflammatory cell infiltration, and the rest no obvious abnormalities. Middle dose group:two mouse lung tissue focal fibrous tissue hyperplasia with inflammatory cell infiltration, and the rest showed no abnormalities. High dose group:two mouse lung tissue focal fibrous tissue hyperplasia with inflammatory cell infiltration, and the rest no obvious abnormalities. Mice in each group pathological classification, statistical analysis, the results were statistically significant (p<0.05).Experimental indicators, compared with the control group the dexamethasone group body weight of mice, lung wet weight was statistically significant (p<0.05); compared with the control group, each group of mice lung index was not statistically significant; blank group comparison, the high-dose group, CC16expression in the lung tissue of mice in the dexamethasone group was significantly higher statistically significant (p<0.05); middle dose group and low dose group, serum levels of dexamethasone Hyp content significantly higher, statistically significant (p<0.05); middle dose group and low dose group, the content of dexamethasone serum levels of IL-8was significantly higher (p<0.05) was statistically significant.Conclusion:In this experiment, ShuangHuangLian powder injection atomization inhalation, the lung tissue of mice have a certain damage. It is an alarming thing. The specific damage mechanism is worth further study. It is not come up with that ShuangHuangLian powder injection and dexamethasone, intravenous can be used for atomizing. The clinician must be in accordance with the drug instructions, and do not change the route of administration at random.

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