本文關(guān)鍵詞：合江縣斯氏肺吸蟲病流行病學(xué)調(diào)查，JAK-STAT和NF-κβ在此病實(shí)驗(yàn)動物肺、肝、腦中的表達(dá)與病理觀察，由筆耕文化傳播整理發(fā)布。

        目的：了解合江縣及毗鄰地區(qū)肺吸蟲病流行現(xiàn)狀；觀察斯氏肺吸蟲病實(shí)驗(yàn)動物模型肺、肝、腦組織超微病理結(jié)構(gòu),觀察JAK-STAT、NF-Kβ通路表達(dá)。方法：溪蟹分部位解剖并計算囊蚴感染率(度),問卷調(diào)查,肺吸蟲病金標(biāo)滲濾試劑盒(DIGFA-Kit)檢測血清抗體,抗體陽性者做肝功檢查；自流行區(qū)采集溪蟹,分離斯氏肺吸蟲囊蚴,經(jīng)腹腔注射感染犬,3月后剖殺,取肺、肝組織并檢獲成蟲備用,肺吸蟲成蟲制備抗原,用腦立體定位儀微量注射肺吸蟲抗原至大鼠大腦皮質(zhì)建立大腦損傷模型,對照組注射生理鹽水,24h后解剖大鼠取腦組織；固定、切片。光鏡下觀察蟲體周圍和抗原注射周圍的組織細(xì)胞反應(yīng),電鏡下觀察超微病理結(jié)構(gòu)改變,免疫組織化學(xué)方法觀察JAK-STAT和NF-Kβ信號通路的表達(dá)活性。結(jié)果：(1)第二中間宿主以鋸齒華溪蟹為主,川南流行區(qū)溪蟹的肺吸蟲囊蚴攜帶率為92.37%(2453／2656),蟲種鑒定為斯氏肺吸蟲(Pagumogonimus Skrjabini),流行區(qū)居民食生蟹率21.53%(208／966),皮下游走性包塊者4.51%(43／966),流行區(qū)人群血清學(xué)DIGFA-Kit檢測肺吸蟲抗體陽性率為4.84%(24／496),川南流行區(qū)人群有生食和半生食溪蟹的習(xí)慣,且感染與鎮(zhèn)村、職業(yè)、年齡有關(guān),差異有統(tǒng)計學(xué)意義(P<0.05),血清肺吸蟲抗體陽性者肝功結(jié)果顯示Y球蛋白升高,白球蛋白比例倒置；(2)斯氏肺吸蟲病肺、肝、腦組織損害的動物模型建立,感染犬肺和肝表面有突起結(jié)節(jié),質(zhì)稍硬,有纖維疤痕形成。HE顯示感染犬支氣管腔有壞死細(xì)胞碎屑或蟲卵,肺泡有蟲卵沉積,卵周有淋巴細(xì)胞浸潤,肺泡囊有陷塌,肺泡隔破壞；感染犬肝切片見壞死灶,嗜酸性粒細(xì)胞浸潤及嗜酸性膿腫形成,壞死周圍有肉芽腫及纖維組織包裹,肝細(xì)胞氣球樣變,萎縮、變性、壞死,肝竇擴(kuò)張；抗原注射大鼠腦血腫周圍組織水腫明顯,且局灶狀壞死,神經(jīng)元皺縮,尼氏小體溶解,周圍出現(xiàn)間隙,神經(jīng)突呈淺淡或消失,可見單核細(xì)胞及膠質(zhì)細(xì)胞反應(yīng)。電鏡顯示感染犬肺可見Ⅰ、Ⅱ型上皮細(xì)胞腫脹、剝脫,細(xì)胞核破壞,線粒體腫脹、嵴斷裂,內(nèi)質(zhì)網(wǎng)擴(kuò)張、空泡樣變；大量滲出液,嗜酸性粒細(xì)胞,單核細(xì)胞浸潤；肺泡隔破壞,細(xì)胞水腫破壞。感染犬肝細(xì)胞水腫,細(xì)胞器破壞,線粒體腫脹、內(nèi)質(zhì)網(wǎng)擴(kuò)張,肝血竇紅細(xì)胞破壞,內(nèi)皮細(xì)胞水腫�？乖⑸浣M大鼠大腦皮質(zhì)神經(jīng)元胞體腫脹,核移位且形狀不規(guī)則,核膜凸凹不平,核質(zhì)溢出；染色質(zhì)為絮狀；線粒體腫脹,粗面內(nèi)質(zhì)網(wǎng)擴(kuò)張呈囊泡化；脂褐素較多。(3)免疫組化顯示正常犬肺中STAT和NF-Kβ弱陽性表達(dá)；感染犬肺可見STAT和NF-Kβ陽性細(xì)胞,免疫陽性物質(zhì)呈棕褐色,NF-Kβ在肺氣道表達(dá)多,STAT在肺實(shí)質(zhì)表達(dá)多,組間存在顯著性差異(X2=476,X2=521,P<0.05)。正常犬肝中STAT和NF-Kβ弱陽性表達(dá)：感染犬實(shí)驗(yàn)組肝可見STAT和NF-Kβ陽性細(xì)胞,以肝細(xì)胞壞死區(qū)明顯,胞質(zhì)和胞核中可見陽性表達(dá),組間存在顯著性差異(X2=405,X2=434,P<0.05)。正常對照組大鼠腦中STAT和NF-Kβ弱陽性表達(dá)：抗原注射組大鼠腦中可見STAT和NF-Kβ陽性細(xì)胞,以大腦皮質(zhì)損傷區(qū)明顯,胞質(zhì)和胞核中見陽性表達(dá),組間存在顯著性差異(X2=476,X2=447,P<0.05)。結(jié)論：(1)肺吸蟲在肺、肝、腦組織中機(jī)械破壞作用和炎癥病理反應(yīng)激活了JAK-STAT、NF-Kβ信號通路的表達(dá)。(2)肺吸蟲病引起組織超微結(jié)構(gòu)改變：細(xì)胞腫脹,線粒體腫脹,內(nèi)質(zhì)網(wǎng)擴(kuò)張。(2)川南流行區(qū)肺吸蟲病的隱性感染依然存在；肺吸蟲病對當(dāng)?shù)鼐用裼绕涫侵行W(xué)生存在著很大的危害：應(yīng)加強(qiáng)肺吸蟲病防治知識的宣傳和教育,制定相應(yīng)的防制措施,阻斷該病在川南地區(qū)的流行。

    Study on the epidemic situation of Paragonimiasis Skrjabini in HeJiang country, research on expression of JAK-STAT、and NF-Kβin lung、liver、brain and changes in pathology in experimental paragonimiasisLI Zhen-lian 1,ZHANG Xi-lin 2, WANG Ying2, CHEN Wen-bi1, QIAN Bao-zhen3,, Sugiyama H4, WANG Guang-xi1※(1.Department of Pathogenic Biology,Luzhou Medical College,Luzhou646000, Sichuan Province,China; 2. Department of Pathogenic Biology,Third Military Medical University;3.Insitute of Biological Engineering, Zhejiang Academy of Medical Science; 4. Institutes of National Health in Japan,Japan)Abstract:objective:To survey epidemic situation, clinical manifestation of paragonimiasis skrjabini in southern Sichuan region Hejiang county. To study expression of JAK-STAT, NF-Kβin the lung,liver, brain and changes in ultrastructural pathology in experimental paragonimiasis.Methods:Epidemic situation of Paragonimiasis Skrjabini in HeJiang was surveyed by anatomizing freshwater crab, calculating the rate of infection metacercar-iae, questionaire, detecting serum antibody with DIGFA-kit. Crabs collected from endemic areas, were used to isolate metacercariae of Paragonimus Skrjabini. The dogs were infected with Paragonimus skrjabini metacercariae by intraperitoneal injection, dissected to obtain the lung tissue, liver tissue, and adult worms 3 months after infection. Rat models of brain damage were established by injecting paragonimus adult worm antigen with stereotactic microinjection apparatus,24h later, rat brain tissues were obtained, fixed, sliced. The reaction of cells around the worms and injecting antigen site were observed with the light microscope and the electron microscope, Expression and activity of the JAK-STAT and NF-K 0 signaling pathway were observed by immunohistochemistry. Results:The second intermediate host was Sinopotamon denticulatum. The Paragonimus skrjabini metacercaria infection rate of freshwater crab was 92.37%(2453/2656).The crab species was identified as Pagumogonimus skrjabini.The rate of eating raw crab in residents was 21.53%(208/966), the most remarkable manifestations was migratory subcutaneous nodules (4.51%), The positive rate of antibody of paragonimiasis was 4.84%(24/496).There are tissue damage in experimental dogs and rat, Nodules and formation of fibrous scar on the surface of lung and liver were observed in the infected dog, HE showed necrotic cell debris or eggs in the bronchial lumen and alveolar, lymphocytes infiltration around the egg, alveolar sacs collapsed, alveolar septa damaged. Necrosis of liver, eosinophil infiltration and eosinophilic abscess formation, necrosis and fibrous tissue wrapped around the granuloma, liver cell ballooning degeneration, atrophy, degeneration, necrosis, hepatocyte nuclear enrichment, sinusoidal expansion were observed in experimental dog.Brain edema around the hematoma in the antigen injection rat, focal necrosi, neuron shrinkage, dissolution of Nissl, surrounded by a gap, disappearance of neurites, reaction of mononuclear cells and glial cells were observed in the antigen injection rat.Electron microscopy showed thatⅠ,Ⅱ-type epithelial cell of lung swelling, exfoliation, nuclear damage, mitochondrial swelling, cristae rupture, expansion of endoplasmic reticulum, vacuole, large effusion, eosinophils, mononuclear cell infiltration, alveolar septal damage, edema and destruction of nearly all cells in the infected dog.Liver cell swelling, organelle damage, mitochondrial swelling, endoplasmic reticulum dilation, red blood cell destruction of the liver sinusoids, endothelial cell edema were observed in the infected dog.Cerebral cortex neurons swelling, nuclear translocation and irregular shape, uneven nuclear membrane, nuclear transfer overflow,, flocculent chromatin, mitochondrial swelling, expansion of rough endoplasmic reticulum, more lipofuscin were observed in the antigen injection rat.Immunohistochemistry showed STAT and NF-Kβlow expression in the lung of normal dog, STAT and NF-Kβpositive cells in infected dog, the positive cells showed brown, NF-Kβmore expression in the airway, STAT more expression in the lung parenchyma, significant differences exist between the two groups (X2=476, X2=521, P<0.05).STAT and NF-Kβlow expression in liver of normal dog, visible positive cells of STAT and NF-Kβin the liver of infected dog, significant necrosis of liver cells, expression can be seen in the cytoplasm and nucleus, significant difference exist between the two groups(X2-405, X2= 434, P<0.05). STAT and NF-Kβlow expression in normal rat brain, visible positive cells of STAT and NF-Kβin the brain of antigen injection rat, cortical damage zone significantly, expression can be seen in the cytoplasm and nucleus, significant difference exist between the groups (X2= 476, X2= 447, P<0.05). Conclusion:Mechanical damage and pathological inflammatory response of the lung fluke activate expression of the JAK-STAT, NF-Kβsignaling pathway in lung, liver of infected dogs and brain antigen injection rats. There are paragonimiasis in HeJiang county South Sichuan, To control paragonmiasis in South Sichuan region, comprehensive control measures and health education should be strengthened.

合江縣斯氏肺吸蟲病流行病學(xué)調(diào)查，JAK-STAT和NF-κβ在此病實(shí)驗(yàn)動物肺、肝、腦中的表達(dá)與病理觀察

1 合江縣斯氏肺吸蟲病流行病學(xué)調(diào)查,JAK-STAT和NF-Kβ在此病實(shí)驗(yàn)動物肺、肝、腦中的表達(dá)與病理觀察3-57    1.1 中文摘要3-6    1.2 英文摘要6-9    1.3 前言10-15    1.4 材料與方法15-22    1.5 結(jié)果22-40    1.6 討論40-48    1.7 結(jié)論48-50    1.8 參考文獻(xiàn)50-56    1.9 英漢縮略詞對照表56-572 致謝57-583 JAK-STAT和NF-Kβ通路在寄生蟲病致病機(jī)制中研究進(jìn)展(綜述)58-72

  本文關(guān)鍵詞：合江縣斯氏肺吸蟲病流行病學(xué)調(diào)查，，JAK-STAT和NF-κβ在此病實(shí)驗(yàn)動物肺、肝、腦中的表達(dá)與病理觀察，由筆耕文化傳播整理發(fā)布。