【摘要】：目的:觀察霧化吸入重組人角質(zhì)細(xì)胞生長因子-2對煙霧吸入性損傷兔氧合作用及炎癥反應(yīng)的影響。方法:將120只新西蘭大耳白兔制成煙霧吸入性損傷模型,隨機分為五組,每組各24只。一組動物致傷后正常飲食飲水,留作空白對照組;其余各組在煙霧吸入性損傷模型達成后開始,每天分別予以霧化吸入5ml PBS及5ml PBS外加1mg/kg、2mg/kg、5mg/kg的rhKGF-2;于實驗組霧化治療1d、3d、5d、7d后,各組各取6只動物麻醉后行耳中動脈血氣分析,心臟采血檢測炎癥指標(biāo)IL-6、IL-8、IL-10及MCP-1,PBS緩沖液灌洗左肺并檢測BALF中炎癥指標(biāo)IL-6、IL-8、IL-10及MCP-1水平,取右下肺下半葉行組織病理學(xué)檢查。結(jié)果:1、整體分析PaO_2、SaO_2發(fā)現(xiàn),藥物因素有顯著作用(P0.001),PaO_2、SaO_2組內(nèi)多重比較發(fā)現(xiàn)1mg組、2mg組及5mg組分別與PBS組相比顯示均有顯著差異(P0.05),且PaO_2組內(nèi)5mg vs 1mg有顯著差異。PH、PaO_2、PaCO_2、SaO_2及HCO_3~-各組整體分析發(fā)現(xiàn)時間因素有顯著作用,PH、PaO_2、PaCO_2、SaO_2各組P0.001,HCO_3~-指標(biāo)P0.05;PH、PaO_2、SaO_2各指標(biāo)組內(nèi)兩兩比較發(fā)現(xiàn)3d vs 1d、5d vs 1d及7d vs 1d有顯著差異(P0.05),PH指標(biāo)組內(nèi)比較7d vs 3d有顯著差異(P0.05),PaCO_2組內(nèi)多重比較發(fā)現(xiàn)3d vs 1d、5d vs 1d有顯著差異(P0.05),HCO_3~-組內(nèi)多重比較發(fā)現(xiàn)5d vs 1d有顯著差異(P0.05)。2、各組動物病理檢查見肺泡腔內(nèi)均有程度不等的炎性滲出及出血表現(xiàn),部分肺泡腔囊狀擴張或萎陷,細(xì)支氣管粘膜出現(xiàn)不同程度的變性、壞死,腔內(nèi)炎性滲出物附著。且隨著時間的變化各組肺泡腔內(nèi)及間質(zhì)內(nèi)中性粒細(xì)胞浸潤、滲出液及出血等情況,均逐漸減輕。且見治療5d、7d后上述變化以5mg組最顯著。3、BALF中的炎癥指標(biāo)IL-6、IL-8及IL-10的整體分析結(jié)果顯示藥物及時間均有顯著作用(P0.05)。藥物因素上,IL-6組內(nèi)多重比較發(fā)現(xiàn),2mg組vs PBS組、5mg組vs PBS組均有差異(P0.05);IL-8組內(nèi)多重比較,1mg組vs PBS組、2mg組vs PBS組、5mg組vs PBS組均有差異(P0.05);IL-10組內(nèi)多重比較,2mg組vs 1mg組有差異(P0.05)。時間因素上,IL-6指標(biāo)組內(nèi)多重比較發(fā)現(xiàn)7d vs 1d有統(tǒng)計學(xué)意義(P0.01),IL-8組內(nèi)多重比較發(fā)現(xiàn)5d vs 1d、7d vs 1d、7d vs 3d均有顯著差異(P0.05),IL-10組內(nèi)多重比較發(fā)現(xiàn)3d vs 1d、7d vs 3d有顯著差異(P0.05);BALF中MCP-1的檢測結(jié)果無統(tǒng)計學(xué)意義(P0.05)。4、血清中的炎癥指標(biāo)檢測結(jié)果未發(fā)現(xiàn)藥物有顯著影響,近一半的血清樣品中未測到IL-6。血清中IL-8、IL-10的整體分析均發(fā)現(xiàn)時間因素有顯著作用(P0.05)。血清IL-8組內(nèi)多重比較發(fā)現(xiàn)5d vs 1d、7d vs 1d有顯著差異(P0.01),7d vs 3d有顯著差異(P0.05);血清IL-10組內(nèi)多重比較發(fā)現(xiàn)7d vs 1d有顯著作用(P0.01)。血清中MCP-1的檢測結(jié)果無統(tǒng)計學(xué)意義(P0.05)。結(jié)論:霧化吸入rhKGF-2治療煙霧吸入性損傷能顯著改善機體氧合作用,減少肺部炎癥反應(yīng),但對全身炎癥反應(yīng)無明顯影響。
[Abstract]:Aim: to observe the effect of nebulized inhalation of recombinant human keratinocyte growth factor-2 on oxygenation and inflammatory response in rabbits with smoke inhalation injury. Methods: 120 New Zealand white rabbits were randomly divided into five groups with 24 rabbits in each group. One group of animals had normal diet and drinking water after injury, and the other groups were given atomized inhalation of 5ml PBS and 5ml PBS respectively every day after the model of smoke inhalation injury was achieved, and the other groups were treated with rhKGF-2; of 1 mg / kg 2 mg / kg + 5 mg / kg rhKGF-2; for 7 days after 1 day of atomization treatment. After anesthesia, the blood gas of middle ear artery was analyzed in 6 animals in each group. IL-6,IL-8,IL-10 and MCP-1,PBS buffer were used to lavage the left lung, and the levels of IL-6,IL-8,IL-10 and MCP-1 in BALF were detected. The lower lobe of right lower lung was taken for histopathological examination. Result: 1, overall analysis of PaO_2,SaO_2 found, Drug factors had significant effect (P0.001) in comparison of the two groups of Pao _ 2C _ 2 and Sao _ P _ 2. Significant differences were found between the 1mg group (2mg) and the 5mg group (P0.05), and the 5mg vs 1mg in the PaO_2 group was significantly different (P < 0.05). The overall analysis of Phapao _ 2 / Paco _ 2C _ 2O _ 2 and HCO_3~- found that there were significant time factors in the whole analysis of each group. P0.001 HCO3HCO3 Index P0.05P0.05 PHPAO2SaO2The results showed that there were significant differences between the three groups (P0.05) in 3 d vs 1 d 5 d vs 1 d and 7 d vs 1 d (P0.05) in PH group there was significant difference between 7 d vs 3D group and 3 d vs 1d group. (P05) significant difference was found in 3 d vs 1d 5 d vs 1d. (P05) significant difference was found in 3 d vs 1d 5 d vs 1d. (P0.05) significant difference was found in 3 d vs 1d 5 d vs 1d in PH index group. (P0.05) significant difference was found between the two groups. (P05) significant difference was found between the two groups. (P05) significant difference was found in 3 d vs 1d 5 d vs 1d in PH group (P0.05). Multiple comparisons within the group showed that there was a significant difference in vs 1d at 5 days (P0.05). Pathological examination showed that there were inflammatory exudation and hemorrhage in alveolar cavity in all groups. Part of alveolar cavity dilated or collapsed, bronchiolus mucosal degeneration, necrosis, intraluminal inflammatory exudate attachment. With the change of time, neutrophil infiltration, exudate and hemorrhage in alveolar cavity and interstitial were gradually alleviated. The results of IL-6,IL-8 and IL-10 in 5mg group showed that the drug and time had significant effect (P0.05). There was significant difference in vs PBS group (P05) in vs PBS 5mg group (P05). There was significant difference between 1mg vs PBS group, 2mg vs PBS group, 5mg group vs PBS group (P0.05) and 2mg group vs 1mg group (P0.05). Significant differences were found in multiple indexes of IL-6 in 7 day vs 1 day group and 7 d vs 1 d 7 d vs 3 d in IL-8 group (P0.05). There was significant difference in MCP-1 in vs 1 d 7 d vs 3 d in IL-10 group (P0.05). The results were not statistically significant (P0.05). 4. No significant effect was found on the inflammatory indexes in serum. IL-6. was not detected in nearly half of the serum samples The whole analysis of IL-8,IL-10 in serum showed that time factor had significant effect (P 0.05). Significant difference was found in serum IL-8 group (P0. 01) on 5 d vs 1 d, 7 d vs 1 d on 7 d vs 3 d (P0.05), and on 7 d vs 1 d in serum IL-10 group (P0. 01). The results of MCP-1 in serum were not statistically significant (P0.05). Conclusion: aerosol inhalation of rhKGF-2 can significantly improve the oxygenation and reduce the pulmonary inflammatory response, but has no obvious effect on systemic inflammatory reaction.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R56

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