【作者】 姚军；

【导师】 王玲；

【作者基本信息】 昆明医学院 ， 病原生物学， 2004， 硕士

【摘要】 目的：通过研究复方中成药制剂杨氏欣痨宁胶囊（YLN）对豚鼠和ICR小鼠结核病模型的抗结核作用，为YLN的临床前研究提供基础研究依据。方法：动物随机分组，分别建立豚鼠和ICR小鼠的结核分枝杆菌H₃₇RV株感染模型，观察以下受试动物指标：体重、脏器病变程度（肉眼观察）、脏器（脾、肺、肝）重量指数、豚鼠脏器结核分枝杆菌定量培养的菌落形成单位（CFU）、ICR小鼠感染H₃₇RV后的死亡时间、半数生存时间(ST₅₀)、存活率、胸腺重量指数、血清细胞因子γ干扰素（IFN-γ）及白细胞介素10（IL-10）的水平。结果：①YLN高、中、低剂量组(1.0g／kg．d^-1，0.5 g／kg．d^-1，0.25 g／kg．d^-1)体重显著大于模型空白对照组，YLN与INH联合用药组豚鼠体重大于INH单用药组（P＜0.05），YLN高剂量组ICR小鼠体重接近于猫爪草组；②YLN各剂量组肉眼观察脏器病变程度均有改善作用（P＜0.05）；③YLN各剂量组脏器重量指数，除YLN低剂量组脾和肝重量指数外，其余各组脏器重量指数显著降低（P＜0.05），INH与YLN联合用药效果优于单用药；④YLN高、中剂量组豚鼠脏器结核分枝杆菌定量培养的CFU数显著低于模型空白对照组（P＜0.05）；⑤YLN各剂量组的ICR小鼠ST₅₀显著长于模型空白对照组，其中YLN高剂量组最显著，YLN高剂量组ST₅₀显著长于猫爪草组，INH与YLN联合用药组存活率接近正常对照组；⑥高剂量YLN能显著增加ICR小鼠胸腺重量指数。⑦高、中、低剂量YLN均能显著提高ICR小鼠结核模型血清IFN-γ水平（p＜0.05），中剂量YLN则显著降低血清IL-10水平（p＜0.05）。结论：各剂量YLN对豚鼠和ICR小鼠结核模型均具有显著抗结核作用，以高、中剂量YLN尤为显著。各剂量YLN均能显著增加结核动物模型的体重和降低脏器病变程度；高、中剂量YLN显著减少豚鼠脏器定量培养CFU数；高剂量YLN具有一定程度的刺激ICR小鼠胸腺增生作用；各剂量YLN具有不同程度的提高ICR小鼠血清IFN-γ水平；中剂量YLN则具有降低血清IL-10水平。YLN与INH合用具有一定的协同作用。更多还原

【Abstract】 Objective In the study we evaluated the effect of YLN capsule , a kind of composite Chinese traditional medicine in animal models on tuberculosis for basic evidence before used clinically. Methods Guinea-pigs and ICR mice were randomly divided into several groups . The guinea-pigs and ICR mice were injected with Mycobacterium (M.) tuberculosis H37RV to establish tuberculosis model, and then to observe indexes including body weight, macroscopical visceral pathogenic degree, visceral weight index ( of spleen , lung and liver), quantitative viscus culture for Mycobacterium tuberculosis in guinea-pigs , time of postinfection death of ICR mice, time of fifty percent survival (ST50), survival rate of ICR mice , and levels of IFN-y and IL-10 in senim of ICR mice . Results (1) Body weight of groups with various doses of YLN (1.0/kg.d"’,0.5 g/kg.d"’,0.25 g/kg.d"1) was heavier than that of blank control group (p<0.05). In guinea-pig , the effect of YLN combined with INH was better than that of INH (p<0.05), and in ICR mice , the effect of high-dose YLN was similar to that of Mao Zhua Cao. (2)Macroscopical visceral pathogenic degree of all groups treated with YLN decreased obviously (p<0.05). (3) Except for the spleen and liver visceral weight indexes of low-dose YLN group, the indexes of all groups treated with YLN were obviously lower than that of blank control group (p<0.05). (4) The CFUs of all groups treated with drugs but low-dose YLN group were obviously lower than that of blank control group(p<0.05). (5) In ICR mice, ST50 of the groups respectively treated with YLN , especially high-dose YLN group, was obviously longer than that of blank control group. The ST50 of group treated with high-dose YLN was longer than that of the group treated with Mao Zhua Cao. Survival rate of the group treated with YLN combined with INH was higher than that of monotherapy groups. (6) Only the thymus weight index of high-dose YLN group increased . (7) Each dose YLN could increase the levels of IFN-y in serum (p<0.05), and mid-dose YLN could obviously decrease levels of IL-10 in serum (p<0.05). Conclusions YLN capsule had an anti-tuberculosis effect on M. tuberculosis H37RV infection in both guinea-pig and ICR mouse model . YLN could increase the weight of tuberculosis model , while decrease thepathogenic degree in the viscerals and CFUs in tuberculosis model , esp. the high dose and the mid-dose YLN. The high-dose YLN increased ICR mouse thymus weight index . Each dose YLN could increase the levels of IFN-y in serum, and the mid-dose YLN could obviously- decrease the levels of IL-10 in serum. We also found YLN had a synergetic effect with INK.更多还原