普萘洛尔和酚妥拉明在神经源性肺水肿大鼠中的作用
Effect of Propranolol and Phentolamine on neurogenic pulmonary edema in rats
摘要目的:探讨普萘洛尔和酚妥拉明在神经源性肺水肿(NPE)大鼠中的作用。方法将120只健康雄性 Wistar 大鼠按随机数字表法分为正常对照组(A 组),NPE 组(B 组),普萘洛尔治疗组(C 组),酚妥拉明治疗组(D 组),各30只。每组又分为造模后0.5 h、6.0 h、24.0 h 3个时间点。除 A 组外,其余各组采用Marmarous 闭合性颅脑损伤模型致大鼠重度、弥散性颅脑损伤。在造模后相应时间点处死大鼠,检测各组肺组织含水量变化,HE 染色观察肺组织病理学改变,酶联免疫吸附法检测血清及支气管肺泡灌洗液(BALF)中神经肽 Y(NPY)及 P 物质(SP)水平,免疫组织化学法检测肺组织 NPY、SP 蛋白表达情况,并进行免疫组织化学评分(IHS)。结果 B 组与 A 组相比,伤后24.0 h 肺组织含水量增高(P ﹤0.05),伤后6.0 h 血清 NPY 水平增高(P ﹤0.05),伤后6.0 h、24.0 h BALF 中 NPY 水平增高(P 均﹤0.05),伤后0.5 h、6.0 h 血清 SP 水平增高(均 P ﹤0.05),伤后0.5 h BALF 中 SP 水平增高(P ﹤0.05),伤后0.5 h、6.0 h、24.0 h 肺组织 NPY 蛋白表达增多(P 均﹤0.05),伤后0.5 h 肺组织 SP 蛋白表达增多(P ﹤0.05)。C 组与 B 组相比,伤后6.0 h、24.0 h 肺组织含水量增高(P 均﹤0.05);伤后6.0 h、24.0 h 血清 NPY 水平增高(P 均﹤0.05),伤后0.5 h、6.0 h 及24.0 h BALF 中 NPY 水平增高(P 均﹤0.05),伤后0.5 h 血清及 BALF SP 水平增高(P 均﹤0.05),伤后6.0 h 肺组织 NPY 蛋白表达增多(P ﹤0.05),伤后0.5 h、6.0 h、24.0 h 肺组织 SP 蛋白表达增多(P 均﹤0.05)。D 组与 B 组相比,伤后6.0 h 血清NPY 水平降低(P ﹤0.05),伤后6.0 h、24.0 h BALF 中 NPY 水平降低(P 均﹤0.05),伤后0.5 h 血清 SP 水平降低(P ﹤0.05),伤后6.0 h、24.0 h 肺组织 NPY 表达增多(P 均﹤0.05),伤后0.5 h 肺组织 SP 蛋白表达增多(P ﹤0.05)。结论酚妥拉明能有效抑制 NPY 和 SP 的分泌,减轻 NPE,普萘洛尔能促使 NPY 和 SP 分泌,加重 NPE。
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abstractsObjective To investigate the effect of Propranolol and Phentolamine on neurogenic pulmonary ede-ma(NPE)in rats. Methods One hundred and twenty male Wistar rats were randomly divided into 4 groups:the con-trol group(group A),the NPE group(group B),the Propranolol treatment group(group C)and the Phentolamine treatment group(group D),30 cases in each group. Diffuse brain injury was induced in the latter 3 groups. The lung wet/ dry ratio was calculated. HE staining was used to measure the histological changes in the lung tissues. The levels of neuropeptide Y(NPY)and substance P(SP)in the serum and the bronchoalveolar lavage fluid(BALF)were detected by enzyme - linked immunosorbent assay(ELISA). The expressions of NPY and SP in the lung tissues were demonstra-ted by immunohistochemical staining,and immunohistochemical scores(IHS)were measured after scarifying the ani-mals at different time points(0. 5,6. 0 and 24. 0 h after injury). Results Compared with group A,water volume in the lungs in group B increased at 24. 0 h(P ﹤ 0. 05);NPY content in the serum was elevated at 6. 0 h,while that in BALF was elevated at 6. 0 h and 24. 0 h(all P ﹤ 0. 05);SP content in the serum was elevated at 0. 5 h and 6. 0 h(all P ﹤0. 05),while that in BALF was elevated at 0. 5 h(P ﹤ 0. 05);The expression of NPY protein in the lung tissue in-creased at 0. 5 h,6. 0 h and 24. 0 h(all P ﹤ 0. 05),while the level of SP protein increased at 0. 5 h(P ﹤ 0. 05). Com-pared with group B,water volume in the lungs in group C was higher at 6. 0 h and 24. 0 h(all P ﹤ 0. 05);NPY concen-trations in the serum were higher at 6. 0 h and 24. 0 h(all P ﹤ 0. 05),while those in BALF were higher at 0. 5 h, 6. 0 h,and 24. 0 h(all P ﹤ 0. 05);SP concentrations in serum and BALF were higher at 0. 5 h(all P ﹤ 0. 05). The ex-pression of NPY protein increased at 6. 0 h(P ﹤ 0. 05),while the levels of SP protein increased at 0. 5 h,6. 0 h and 24. 0 h(all P ﹤ 0. 05). Compared with group B,the level of NPY in serum in group D was lower at 6. 0 h,and that in BALF was lower at 6. 0 h and 24. 0 h(all P ﹤ 0. 05). The level of SP in serum was lower at 0. 5 h(P ﹤ 0. 05). The ex-pression of NPY protein decreased at 6. 0 h and 24. 0 h(all P ﹤ 0. 05),while the levels of SP protein decreased at 0. 5 h(P ﹤ 0. 05). Conclusions Phentolamine is effective in reducing NPE through reduction of NPY and SP,while propranolol can stimulate the release of NPY and SP to aggravate NPE following traumatic brain injury in rats.
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