【作者】 向瑞平；

【导师】 王小龙；

【作者基本信息】 南京农业大学 ， 临床兽医学， 2002， 博士

【摘要】 肉鸡肺动脉高压综合征(pulmonary hypertension syndrome，PHS)是当今世界各国肉鸡业中的一大难题，常常发生在海拔3000米左右的高原地区，主要以肺动脉高压、右心室肥大、心脏衰竭和腹水等症状为特征。近年来，在低于海拔1000-2000米甚至低于海平面的一些地区也常见肉鸡发生类似的疾病。肉鸡PHS是一个复杂的综合征，在美国肉鸡PHS的死亡率为2-5％，甚至高达10％以上，每年因此病造成的经济损失达1亿多美元。在世界范围内的其发病率为4.2％，每年约有70亿肉鸡遭受此病的侵害，估计全世界因此病所造成的经济损失每年达10亿美元。从1986年起我国十几个省市也陆续报道了本征，其死亡率为1-30％不等，损失惨重。因此引起了国内外学者对该病的广泛关注。为了攻克这一威胁肉鸡业的世界性难题，国内外许多学者潜心致力于PHS的病因、病理发生和防制的研究。多数学者认为导致肺动脉高压的主要因素是由于在遗传育种中片面追求高的生长速率，其机体代谢加强和对氧的需要量剧增，致使组织代谢性缺氧，引起血液红细胞压积、血液粘度、红细胞脆性和血容量增加等血液流变力学的变化。但更深层次的发病机制还不十分明了，本研究从肉鸡肺动脉高压引起的肺血管结构变化、体内自由基变化的不同角度，进一步研究其发病机制，寻求不同的防制手段和方法。 试验Ⅰ PHS肉鸡肺血管肌化分型方法和血管密度变化。随机抽取12羽与缺氧有关的肺动脉高压综合征(PHS)自然病鸡和12羽同种、同龄健康AA肉鸡，用组织形态学方法对患PHS肉鸡和健康肉鸡肺细小动脉结构变化进行定量检测和比较分析，参照哺乳动物肺动脉血管肌型化分型方法，提出了家禽肺动脉三型血管的分型方法：即血管具完整的内外两层弹力板者为肌性动脉(MA)；在单层弹力板内侧又出现一层不完整的弹力板者为部分肌性动脉(PMA)；仅有一层弹力板者为非肌性动脉(NMA)。结果显示：患PHS肉鸡的肺细小动脉血管管壁面积与管总面积之比(WA／TA)、中膜厚度与管外径之比均极显著高于健康肉鸡(P＜0.01)。对直径小于60μm和直径小于200μm的肺微细动脉的末稍厚壁血管百分率和三型血管占位比例进行测定，结果患PHS肉鸡的肌化百分率也极显著高于健康肉鸡(P＜0.01)。血管密度则极显著性降低 博士学位论文；肺动脉高压肉鸡肺小动脉肌型化和自由基变化的研究（P删．01）；组织病理学检查显示，血管内膜及中膜细胞增生、肥厚。 试验11 高钠所致急性和慢性肺动脉高压。为了进一步探讨肉鸡肺动脉高压综合征（PHS）的发病机制，将240羽1日龄健康＊肉鸡随机均分为对照组（C）、试验1组（T；）和试验＊组门；），从 8日龄起分别按 0，6 0 0和 1二 0 0 mg厂’饮水的浓度添加Na”于饮水中，全程动态观察和测试各组肉鸡临床表现、PHS发病率、右心与全心重量比（RV八V）、红细胞压积uCV）、红细胞滤过指数和血容量，用组织形态学方法对各组患鸡与对照鸡的肺细小动脉结构变化进行动态定量检测和比较分析。结果显示：饮水高钠成功诱发了肉鸡皿S，并显著升高了肉鸡叫S发病率、RWTV和NV（Ac．05 L35和 42日龄时，试验组患MS肉鸡肺血管肌化百分率（％MA和％WTPV）、管壁面积与管总面积之比仰A／TA）和平均中膜厚度（mMTPA）显著增加叫HO．05＼ 血管非肌化百分率（％NMA）则显著降低（HO．05），但红细胞滤过指数和血容量无变化。在 28 日龄以前，试验组叩S患鸡的红细胞滤过指数和血容量显著增加（A0．“八 而血管删A、％WTPV、WA／TA、mMTPA和％NMA无显著差异。 试验ill 维生素 C对肺血管肌化的作用。380羽M商品肉鸡随机分为 A组（100羽）和 B、C、D和 E组（各 70羽厂 参试鸡 14日龄前按常规饲养。14日龄后 A组鸡仍按常规饲养，而 B、C、D和 E组鸡舍温按每日 1－2’C由 25’C逐步降至 12’C，同时 D和E组在日粮中按1．sing·kg“’的剂量添加三碘甲状腺原氨酸门；）以诱发肉鸡肺动脉高压综合征OHS）；C和 E组在日粮中以 5m mg·kg”‘的剂量添加维生素 C以现察其效果，至试验结束。记录每周各组鸡群平均体重、采食量和叫S发病数；每周每组随机抽取10只鸡进行剖杀、采血和采肺组织以测定其红细胞压积（PC们和厚壁外周血管百分率（％TWPV）。结果表明：低温和 T；能显著增加 PHS发病率、PCV值和 TWPV百分率（P＜0．01），显著抑制肉鸡的增重（P＜0．05），低温显著增加采食量而儿则显著抑制采食量仔q．01h 同时，分别在低温或低温加L的条件下，添加维生素C能显著抑制叫S发病率和＊W百分率的上升（P＜0．01），但未能改变肉鸡的盯V值、增重、采食量和饲料转换率O叩．05L 试验IV PHS患鸡自由基的变化及清除．为了揭示自由基在肉鸡肺动脉高压综合征（PHS）病理发生过程中的作用，本试验将 380羽M商品肉鸡随机分为 A组 100羽；B、C、D和 E组各 7 0 l，14日龄前常规饲养。14日龄S B、C、D和 E组舍ja按每日1－2℃由 25℃逐步降至 12℃，同时日粮中按 1．5 mg·kg”‘的剂量添加 T；以诱发 PHS；C和 D组在日粮中分别按 500 mg·kg“‘和 100 mg·kg”‘的剂量添加维生素 C?更多还原

【Abstract】 Pulmonary hypertension syndrome (PHS) in broiler chickens poses a serious problem to the international poultry industry, and is an important cause of mortality that has been reported from many parts of the world. For broilers kept at altitudes of approximately 3000m, the onset of pulmonary hypertension, cardiac hypertrophy, heart failure, and oedema leading to PHS has been described. More recently similar symptoms and mortality rates were reported in broilers reared at lower altitudes of 1000 to 2000m and at altitudes down to sea level. A survey in the United States showed that PHS accounts for over 25% of annual broiler losses. An incidence of PHS of 5-10% was reported in China. A global incidence of 4-5% PHS has been reported and, at today’s market prices, this mortality represents a cost to the industry of about one billion $US annually. It has been suggested that the fast-growing modern broiler is particularly susceptible to PHS, because rapid growth causes an increased demand for oxygen, which forces the heart to maintain an elevated cardiac output. The resulting increase in blood pressure within the pulmonary circulation can cause hypertrophy of the right ventricle and eventually congestive heart failure. This pathogenesis for PHS includes increased oxygen requirements by body tissues and low oxygen tensions in arterial blood. Further pathologic mechanism is not clear. The present study was conducted to further evaluate the pathogenesis of the acute and chronic forms of PHS, the muscularization in pulmonary arterioles and the changes of free radicals in broilers with PHS, and to obtain the methods preventing PHS.Test I , the changes of the muscularization and density in pulmonary arterioles in field cases of broilers with PHS induced by hypoxia. Twelve field cases with pulmonary hypertension syndrome in broilers due to hypoxia and twelve healthy birds from the same flock as control were randomly selected for histomorphological evaluation of pulmonary arterioles. The histopathological alterations of pulmonary arterioles in broilers with PHS and in controls were measured and analyzed. Refering to classified methods of pulmonary vascular muscularity for mammals, the classified methods of pulmonary vascular muscularity for birds were proposed. The arterioles with complete internal andexternal elastic lamina were identified as the muscular arterioles(MA); ones with partially internal elastic lamina in complete external elastic lamina were identified as the partially muscular arterioles(PMA); ones with a single elastic lamina were identified as the non-muscular arterioles(NMA). The result indicated that the ratio of vessel wall area to total vessel area (WA/TA) and the ratio of medial thickness in pulmonary arteries to blood vessel diameter were more significantly increased (P<0.01) in sick birds than in healthy birds and that the percentage of pulmonary vascular muscularity were also significantly increased (P<0.01) by measuring the percentage of thick-walled peripheral lung vessels at <200 U m and <60 y m . The density of pulmonary artery were significantly decreased (P<0.01). Histopathological observation showed the intimal cellular proliferation and medial hypertrophy.Test II, acute and chronic pulmonary hypertension induced by excess sodium. Tostudy the pathogenesis of pulmonary hypertension syndrome (PHS) in broilers, two hundred and forty 1-day-old Arbor Acres commercial broilers were divided randomly into control (C) and experimental (T\ and T2 ) groups that were treated with 0, 600 and 1200 mg-L-1 Na+ from NaCl (sodium chloride) in their drinking water respectively from 8 to 42 days of age. Experimental and control birds were selected for the dynamic evaluations of the signs and incidence of PHS, the ratio of right ventricle to total ventricle (RV/TV), packed cell volume (PCV), filtration index of red cell, blood volume and histopathological alteration of pulmonary arterioles in different groups respectively at 9,14,21,28, 35 and 42 day of age. The results indicated that the high sodium更多还原