臺灣博碩士論文加值系統

本實驗以原位雜交技術偵測豬生殖與呼吸綜合症病毒 ( Porcine reproductive and respiratory syndrome；PRRSV ) 台灣分離株MD-001於實驗感染無特定病原之2日齡不吃初乳初生仔豬及4-5週齡保育豬，病毒與細胞激素IL-1、IL-2、TNF- 及IFN- mRNA於攻毒後不同時間之分佈情形。將7隻無PRRSV之無特定病原之初生仔豬及35隻4-5週齡無PRRSV之無特定病原保育豬分別隨機分成6隻攻毒組/ 1隻對照組及18隻攻毒組/17隻對照組。以鼻內接種的方式分別於二鼻孔內各接種105 TCID50 / ml病毒力價之病毒液0.5 ml；對照組豬隻則以相同方式接種未感染病毒之細胞培養液。在2日齡出生仔豬，對照組豬隻於第0天，攻毒組豬隻分別於接種後第1、3、7天予以安樂死。在4-5週齡保育豬，對照組豬隻分別於接種後第0、3、7、14、21天，攻毒組豬隻則於攻毒後第1、3、7、14、21天予以安樂死。原位雜交所用之病毒探針為與PRRSV之第7開放毒碼區互補之RNA片段，大小為433bp，並以DIG標的。細胞激素的RNA探針也標以DIG，大小依序為IL-1480bp、IL-2 401bp 、TNF- 340bp及IFN-367 bp 。在小豬感染後第1天，即可在肺臟及受檢的支氣管、頸部、肩胛前、胃及腸繫膜淋巴結偵測到PRRS病毒之陽性雜交訊息。在肺臟，病毒表現隨攻毒時間的延長而增加，淋巴結則表現各不一。在細胞激素的表現方面，在肺臟及頸部、肩胛前、胃、腸繫膜淋巴結，TNF-及IFN-mRNA陽性雜交訊息有隨病毒增加而上升之趨勢，但是病毒與細胞激素出現之位置並無明顯相關性。4-5週齡保育豬，在肺臟，病變於攻毒後7日逐漸出現，病毒及細胞激素之陽性訊息微弱，這些陽性雜交訊息散佈於病變之間，細胞激素並無隨病毒表現量增加而上升之趨勢。另外在支氣管淋巴結，於攻毒後第3天病毒量達最高，之後隨攻毒天數增加而減少， IFN-及IL-1表現量也有隨之降低的趨勢。另外於攻毒後14及21天，可在小腸組織之黏膜層及黏膜下層偵測到較多PRRSV及IFN-陽性雜交訊息。肺臟之陽性細胞於型態學上近似於肺泡及間質巨噬細胞及少量單核細胞；淋巴組織內之陽性細胞則近似樹枝狀細胞、巨噬細胞及少部分單核細胞，陽性細胞位置主要出現在髓質及生發中心周圍。由實驗結果推知小豬急性感染PRRSV後病毒複製能力強，細胞激素TNF-及IFN- 表現有隨病毒量增加而上升之趨勢，其雖有細胞激素的表現，但並無嚴重病變之形成。在4-5週齡保育豬感染PRRSV後，病變雖於後期出現，但病毒與細胞激素的表現就陽性細胞數目而言，皆較初生小豬減少許多且較混亂及無明確的趨勢。此外本實驗更進一步證實PRRSV感染後期可能會經由消化道排出之推論。

The aim of this study was to determine the relationship between the organ distribution of porcine reproductive and respiratory virus ( PRRSV ) and the cytokine IL-1, IL-2, TNF-, and IFN- mRNA expression in two experimental PRRSV-infected pig groups by in situ hybridization. Seven 2-day-old PRRSV-free and 35 4 to 5-week-old, SPF pigs were randomly allocated to the PRRSV-infected group/control group at ratio 6/1 and 18/17, respectively. The PRRSV-infected and control animals were intranasally inoculated with 0.5 ml 105 PRRSV TCID50 /ml or culture medium per nostril. Two-day-old control and PRRSV-infected pigs were euthanatized at 0 and at 1, 3, 7 days post infection ( DPI ), respectively. Four to 5-week-old control pigs and PRRSV-infected pigs were euthanatized at 0, 3, 7, 14 and 21DPI, and at 1, 3, 7, 14 and 21 DPI, respectively. The virus RNA probe for in situ hybridization was a 433 bp, DIG-labeled fragment corresponding to the open reading frame 7 of the PRRSV. The cytokine RNA probes for in situ hybridization were DIG-labeled with a size of IL-1480bpIL-2 401bpTNF-340bpandIFN-367bpIn the 2-day-old pigs specific viral signals were detected in the lungs and the various lymph nodes, including bronchialprescapularcervicalgastric, and mesenteric lymph nodes. In the lungs, the number of PRRSV-infected cells increased with time; however, it appeared to be unrelated in the lymph nodes. Specific TNF- and IFN- signals increased with the raising number of PRRSV-infected cells in the prescapular gastric, and mesenteric lymph nodes, nevertheless, there was no spatial location relationship between the PRRSV-infected and cytokine -expressing cells. All of the PRRSV and cytokine signals in 4 to 5-week-old pigs were weaker than those of the neonatal group. These signals were scattered in the interstitial lesions of the lung. In bronchial lymph node, the positive PRRSV-infected cells reached the highest numbers at 3 DPI, and decreased with time. In the meantime, similar trend was present in TNF-and IFN- mRNA-expressing cells. PRRSV and IFN- positive signals were detected in the intestinal mucosa and submucosa at 14 and 21 DPI. Positive signal-exhibiting cells morphologically resembled alveolar and interstitial macrophages and other mononuclear inflammatory cells in the lungs; and resembled macrophages, dendritic cells, and other mononuclear cells in the medullay and peripheral germinal center of the lymph nodes. The results suggest: 1) in the neonatal pig group, there was a similar trend of change number between viral-infected and TNF-and IFN-mRNA expressing-cells, but there was no locational relationship between virus-infected and cytokine-expressing cells; 2) in the 4 to 5-week-old pig group, cytokine mRNA expressing-cells were less than those in the neonatal group, and there were no particular positional correlation among PRRSV-infected cells, cytokine-expressing cells, and lesion formation; 3) virus shedding from alimentary tract was possible at the late infection stage.

中文摘要-------------------------------------------------------------------------------I
英文摘要-------------------------------------------------------------------------------III
目錄-------------------------------------------------------------------------------------V
圖次------------------------------------------------------------------------------------VII
表次------------------------------------------------------------------------------------IX
第一章 緒言-------------------------------------------------------------------------1
第二章 文獻探討-------------------------------------------------------------------3
第1節 豬生殖與呼吸綜合症----------------------------------------------------3
1-1 歷史背景及發生概況---------------------------------------------------3
1-2 病毒特性------------------------------------------------------------------4
1-3 臨床症狀及病理變化---------------------------------------------------6
1-4 致病機制-----------------------------------------------------------------10
第2節 豬生殖與呼吸綜合症對免疫系統的影響---------------------------13
2-1 對免疫細胞之作用-----------------------------------------------------13
2-2 細胞性免疫--------------------------------------------------------------15
2-3 體液性免疫--------------------------------------------------------------17
2-4 與其他病原之關係-----------------------------------------------------18
2-5 細胞激素之表現--------------------------------------------------------21
第3節 細胞激素的調控與疾病之關係---------------------------------------23
第4節 原位雜交在偵測病毒與細胞激素的應用---------------------------26
第三章 材料與方法---------------------------------------------------------------30
第1節 緒言------------------------------------------------------------------------30
第2節 實驗設計------------------------------------------------------------------31
第3節 實驗動物------------------------------------------------------------------31
第4節 核酸探針之製備---------------------------------------------------------32
4-1 細胞激素核酸探針之製備--------------------------------------------32
4-2 病毒核酸探針之製備---------------------------------------------------37
第5節 原位雜交-----------------------------------------------------------------40
第6節 陽性細胞數目計算之方式----------------------------------------------41
第四章 結果------------------------------------------------------------------------44
第1節探針基因之選殖----------------------------------------------------------44
1-1 細胞激素探針基因之選殖-------------------------------------------44
1-2 病毒基因探針之選殖-------------------------------------------------44
第2節 細胞激素在PRRSV感染初生仔豬表現之情形-------------------44
2-1 肺臟組織----------------------------------------------------------------44
2-2 支氣管淋巴結----------------------------------------------------------45
2-3 頸部淋巴結-------------------------------------------------------------46
2-4 肩胛前淋巴結----------------------------------------------------------46
2-5 胃淋巴結----------------------------------------------------------------47
2-6 腸繫膜淋巴結----------------------------------------------------------47
2-7 細胞激素之表現與病毒的關係-------------------------------47
第3節 細胞激素在PRRSV感染4-5週齡豬隻表現之情形---------------48
3-1 肺臟組織----------------------------------------------------------------48
3-2 扁桃腺-------------------------------------------------------------------49
3-3 顎下淋巴結-------------------------------------------------------------49
3-4 支氣管淋巴結----------------------------------------------------------50
3-5 腸繫膜淋巴結----------------------------------------------------------50
3-6 細胞激素之表現與病毒的關----------------------------------50
第4節 腸道組織病毒與細胞激素表現之變化------------------------------ 51
第五章 討論-------------------------------------------------------------------------86
參考文獻------------------------------------------------------------------------------95

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