發(fā)布時間：2018-08-31 08:01

【摘要】： 【目的】 真菌性鼻竇炎可分為“侵襲性”和“非侵襲性”兩大類型。非侵襲性與侵襲性區(qū)別在于真菌菌絲是否侵入黏膜、黏膜下、血管、骨質(zhì)等組織結(jié)構(gòu)中,侵襲性真菌感染一旦發(fā)生,往往預(yù)后不佳,其死亡率和致殘率均高。國內(nèi)外對真菌性鼻竇炎的研究不多,真菌性鼻竇炎特別是侵襲性真菌性鼻竇炎的發(fā)病機制不明,動物模型的建立可以作為后期研究的基礎(chǔ),僅國外制成非侵襲性真菌性鼻竇炎動物模型,未見有侵襲性真菌性鼻竇炎動物模型制作成功報道。本實驗探討實驗性真菌性鼻竇炎動物模型的制備方法尤其是侵襲性真菌性鼻竇炎動物模型的制備和非侵襲性真菌性鼻竇炎動物模型的手術(shù)療效。為真菌性鼻竇炎的發(fā)病機制,病理生理,治療及預(yù)后等研究提供良好的實驗性模型。 【方法】 一非侵襲性真菌性鼻竇炎動物模型的制備一定量煙曲菌接種免疫功能正常兔的上頜竇,以上頜竇自然開口是否給予封閉及鼻竇黏膜是否給與劃傷的不同處理方法為分組標準,以未有煙曲菌接種組給予相同上頜竇自然開口及鼻竇黏膜的處理方法為對照,分為空白對照組、假手術(shù)組、黏膜劃傷組、竇口阻塞組、僅注入煙曲菌組、注入煙曲菌并給予黏膜劃傷組、注入煙曲菌加竇口阻塞組7組。于接種后14天及28天觀察各組實驗動物的一般情況,上頜竇內(nèi)情況,分泌物真菌培養(yǎng),分泌物涂片及黏膜病理檢查,以分泌物真菌培養(yǎng)、分泌物涂片及病理檢查結(jié)果為判定標準,研究各組制模成功率。 二侵襲性真菌性鼻竇炎動物模型的制備給予免疫抑制劑造成兔免疫功能低下,一定量煙曲菌接種已制成免疫功能低下兔的上頜竇,不同竇口處理方式及免疫抑制劑處理為分組標準,未有給予免疫抑制劑而給予相同上頜竇自然開口處理為對照,分為竇口開放組(環(huán)磷酰胺組、地塞米松組、對照組)3組,竇口封閉組(環(huán)磷酰胺組、地塞米松組、對照組)3組,共6組。于接種后28天觀察各組實驗動物的一般情況,上頜竇內(nèi)情況,分泌物真菌培養(yǎng)、分泌物涂片、黏膜病理檢查及影像學(xué)檢查,以分泌物真菌培養(yǎng)、影像學(xué)檢查、分泌物涂片及病理檢查結(jié)果為判定標準,研究各組制模成功率。 三非侵襲性真菌性鼻竇炎的動物模型手術(shù)療效的研究制成非侵襲性真菌性鼻竇炎動物模型后,按擴大上頜竇自然開口和保持原竇口大小開放上頜竇自然口不同手術(shù)方式為分組標準,分為上頜竇自然口擴大組和上頜竇自然口開放組2組。以觀察竇腔情況、竇口是否開放,是否有膿性分泌物、分泌物真菌培養(yǎng)、分泌物涂片及病理檢查結(jié)果為判定標準,觀察術(shù)后6周后兩組術(shù)式的不同療效。 【結(jié)果】 一非侵襲性真菌性鼻竇炎動物模型的制備實驗動物接種煙曲菌14天后,注入煙曲菌加竇口阻塞組上頜竇分泌物煙曲菌培養(yǎng)陽性率88.9%(8/9側(cè)),28天后注入煙曲菌加竇口阻塞組上頜竇分泌物煙曲菌培養(yǎng)陽性率77.8%(7/9側(cè))。所有病理結(jié)果均未顯示煙曲菌侵襲上頜竇黏膜及組織,即未有侵襲性真菌性鼻竇炎發(fā)生。 二侵襲性真菌性鼻竇炎動物模型的制備免疫抑制劑環(huán)磷酰胺加煙曲菌接種并上頜竇口阻塞組28天后上頜竇分泌物煙曲菌培養(yǎng)陽性率為100.0%(8/8側(cè));免疫抑制劑地塞米松加煙曲菌接種并上頜竇口阻塞組28天后上頜竇分泌物煙曲菌培養(yǎng)陽性率為100.0%(8/8側(cè));未給予免疫抑制劑接種煙曲菌并上頜竇阻塞組煙曲菌培養(yǎng)陽性率為87.5%(7/8側(cè));各組上頜竇黏膜PAS染色病理檢查,均未見上頜竇黏膜及組織內(nèi)煙曲菌侵襲,即未有侵襲性真菌性鼻竇炎發(fā)生。 三非侵襲性真菌性鼻竇炎的動物模型手術(shù)療效的研究非侵襲性真菌性上頜竇炎制模成功后,按擴大上頜竇自然開口和保持原竇口大小開放上頜竇自然口不同手術(shù)方式為分組標準,6周后觀察竇口是否開放及竇腔內(nèi)有無膿性分泌物,上頜竇內(nèi)分泌物并真菌培養(yǎng),黏膜組織送病理檢查。擴大上頜竇自然開口對實驗性真菌性上頜竇炎的有效率達83.3%(10/12側(cè)),開放上頜寞竇口對實驗性真菌性上頜竇炎的有效率達33.3%(4/12側(cè))。 【結(jié)論】 兔上頜竇注入一定量煙曲霉菌并給予上頜竇自然口阻塞可成功制成非侵襲性真菌性鼻竇炎動物模型。 給予免疫抑制劑可造成兔免疫低下,在實驗兔免疫功能低下狀態(tài)下于上頜竇內(nèi)接種一定量煙曲菌并給予上頜竇自然口阻塞未能制成侵襲性真菌性鼻竇炎動物模型,侵襲性真菌性鼻竇炎動物模型的制備方法有待探討。 上頜竇竇口擴大術(shù)對實驗性真菌性上頜竇炎的療效較上頜竇竇口開放術(shù)(保持原竇口大小)好。
[Abstract]:[Objective]
Fungal sinusitis can be divided into "invasive" and "non-invasive" types. The difference between non-invasive and invasive fungal mycelia is whether fungal mycelia invade the mucosa, submucosa, blood vessels, bone and other tissue structures. Once invasive fungal infection occurs, its prognosis is often poor, and its mortality and disability rate are high. The pathogenesis of fungal sinusitis, especially invasive fungal sinusitis, is unknown. Animal models can be used as the basis for later research. Only non-invasive fungal sinusitis animal models were made abroad, and no invasive fungal sinusitis animal models were successfully reported. The preparation of animal models of fungal sinusitis, especially the preparation of animal models of invasive fungal sinusitis and the surgical effect of non-invasive fungal sinusitis, provide a good experimental model for the pathogenesis, pathophysiology, treatment and prognosis of fungal sinusitis.
[method]
The maxillary sinuses of rabbits with normal immune function were inoculated with Aspergillus fumigatus. The maxillary sinuses were divided into two groups according to whether the natural ostium of maxillary sinus was sealed and whether the nasal sinus mucosa was scratched or not. The maxillary sinuses were inoculated with Aspergillus fumigatus and the nasal sinus mucosa without Aspergillus fumigatus. The control group was divided into seven groups: control group, sham operation group, mucosal scratch group, sinus ostium obstruction group, Aspergillus fumigatus group, Aspergillus fumigatus group and mucosal scratch group, Aspergillus fumigatus plus sinus ostium obstruction group. Secretory smears and Mucosal pathological examination were used to study the success rate of each group.
Immunosuppressive agents were given to the rabbits to induce immunodeficiency. A certain amount of Aspergillus fumigatus was inoculated into the maxillary sinuses of the rabbits with immunodeficiency. Different treatments of ostium and immunosuppressive agents were used as grouping criteria. The same natural ostium of maxillary sinuses was given without immunosuppressive agents. They were divided into three groups: the open sinus ostium group (cyclophosphamide group, dexamethasone group, control group), the closed sinus ostium group (cyclophosphamide group, dexamethasone group, control group) and the closed sinus ostium group (cyclophosphamide group, dexamethasone group, control group). The success rate of mold making in each group was studied according to the results of secretion fungi culture, imaging examination, secretion smear and pathological examination.
The animal models of non-invasive fungal sinusitis were established and divided into maxillary sinus natural ostium enlargement group and maxillary sinus natural ostium enlargement group according to the different surgical methods of enlarging the natural ostium of maxillary sinus and keeping the size of the original ostium of maxillary sinus. Group A: To observe the sinus cavity, whether the ostium is open, whether there is purulent secretion, secretion fungus culture, secretion smear and pathological examination results as the judgment criteria, to observe the two groups after 6 weeks of different surgical effects.
[results]
The positive rate of Aspergillus fumigatus culture in maxillary sinus secretion was 88.9% (8/9 sides) in the Aspergillus fumigatus plus ostium obstruction group 14 days after inoculation. The positive rate of Aspergillus fumigatus culture in maxillary sinus secretion was 77.8% (7/9 sides) in the Aspergillus fumigatus plus ostium obstruction group 28 days after inoculation. No Aspergillus fumigatus invaded the mucosa and tissues of the maxillary sinus. No invasive fungal sinusitis occurred.
The positive rate of Aspergillus fumigatus culture in maxillary sinus secretion was 100.0% (8 / 8 sides) 28 days after inoculation with cyclophosphamide plus Aspergillus fumigatus and the positive rate of Aspergillus fumigatus culture in maxillary sinus secretion 28 days after inoculation with dexamethasone plus Aspergillus fumigatus and maxillary sinus ostium obstruction The positive rate was 100.0% (8/8 sides), the positive rate of Aspergillus culture was 87.5% (7/8 sides) in the group without immunosuppressive inoculation and maxillary sinus obstruction, and no invasive fungal sinusitis was found in maxillary sinus mucosa and tissue by PAS staining.
Study on the surgical effect of three non-invasive fungal sinusitis animal models The effective rate of enlarging the natural ostium of maxillary sinus for experimental fungal maxillary sinusitis was 83.3% (10/12 sides) and that of opening the ostium of maxillary sinus for experimental fungal maxillary sinusitis was 33.3% (4/12 sides).
[Conclusion]
Non-invasive fungal sinusitis animal models were successfully established by injecting a certain amount of Aspergillus fumigatus into the maxillary sinus and obstructing the natural mouth of the maxillary sinus.
Invasive fungal sinusitis animal model could not be established by inoculating a certain amount of Aspergillus fumigatus into maxillary sinus and obstructing the natural mouth of maxillary sinus in experimental rabbits. The preparation method of the animal model of invasive fungal sinusitis remains to be explored.
The effect of maxillary ostium enlargement on experimental fungal maxillary sinusitis is better than that of maxillary ostium enlargement.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R763;R-332

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