月华胶囊对结核杆菌感染小鼠致病指数、病理形态等影响的实验研究
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摘要
目的：观察①月华胶囊对结核杆菌感染小鼠体温、体重、进食量等主要临床症状的影响；②月华胶囊对结核杆菌感染小鼠主要脏器致病指数的影响；③月华胶囊对结核杆菌感染小鼠病理形态改变的影响。
方法：经尾静脉注射H37Bγ建立NIH小鼠感染结核杆菌模型。随机设立①正常组、②模型组、③月华胶囊低剂量组、④月华胶囊中剂量组、⑤月华胶囊高剂量组、⑥西药化疗(利福平+异烟肼+吡嗪酰胺)组,⑦月华胶囊联合西药化疗组。通过灌胃给药30天。观测：①主要症状改变：体温、体重、进食量；②致病指数：肺脏病变指数、脏器重量指数；③病理改变：肺、肝、脾、心、肾病理变化。
结果：模型组与正常组比较各项指标差异均有显著性差异。各组之间比较：①用药各组临床症状明显优于模型组(P<0.01,P<0.05),其中联合组效果最佳,与月华胶囊各组及西药组比较差异均有显著性意义(P<0.01,P<0.05),其与正常组比较差异无显著性；月华胶囊中剂量组优于高、低两个剂量组(P<0.01,P<0.05)。②用药各组肺脏病变指数均较模型组低(P＜0.01,P<0.05),且联合组优于单独用药各组(P<0.05),单独用药各组间比较差异无显著性意义。③各用药组胸腺与肺指数明显优于模型组(P<0.01,P<0.05),联合用药组较单独用药组效果更好(P<0.05)；用药各组肝、脾指数较模型组低,用药各组之间比较无显著差异；各组肾指数比较差异无统计学意义。④用药各组与模型组比较,病理损害均有不同程度的改善(P<0.01,P<0.05)；联合用药组效果最佳,中剂量组次之,与各组之间比较有显著性差异(P<0.01,P<0.05)。
结论：①月华胶囊能改善结核杆菌感染小鼠主要临床症状及致病指数,能显著降低结核杆菌对小鼠脏器的病理损害。②月华胶囊中剂量的效果最好。③月华胶囊与西药联合运用,效果优于单独用药组,说明两者间具有一定的协同作用。
Objective:Observe①the effect of yuehua capsules on important symptoms such as body temperature, weight and repast of rats with tuberculosis.②the effect of yuehua capsules on disease indexes of important organs of rats with tuberculosis.③the effect of yuehua capsules on pathomorphological change of rats with tuberculosis.
Methods:The NIH rats models infected tuberculosis were established by injecting H37RV into the tail vein of rats, which were grouped into the model group, western chemotherapy medicine (INH+RFP+PIA) group, Yuehua capsules high-dose group, Yuehua capsule mid-dose group, Yuehua capsule lower-dose group, Yuehua capsules & western chemotherapy medicine group, and the normal group was made before the models were built. The rats were fed by way of gavage with corresponding medicine or distilled water for 30 days continuously. The following targets were observed:①the change of important symptoms such as body temperature, body weight and food-intake.②the disease indexes such as lesion index of lung and weight index of visceral organs.③the pathomorphological change of important visceral organs such as lung, liver, spleen, kidney and heart.
Results:Compared with the normal group, all targets of the model group had evident difference (P<0.01,P<0.05). Compared with every group, groups that used medicine were better than the model group(P<0.01,P<0.05), especially yuehua capsules & western chemotherapy medicine group was best among them, and compared with the normal group, there was no evident difference, but in three yuehua capsules groups, the mid-dose group was best among them(P<0.05).②Compared with the model group, the lung disease indexes of every group was lower than that of it(P<0.01,P<0.05), and the Yuehua capsules & western medicine group was better than that of groups used single medicine, in which there was no difference obviously.③Compared with the model group, the disease indexes of thymus and lung of else every group were superior to that of the model group(P<0.05),and combined group was better than that of the western medicine group or yuehua capsules groups(P<0. 05).and there was no significant difference between combined group and the model group. Compared with model group, the indexes of liver and spleen of all groups were lower than that of the model group, but there was no evident difference among groups used medicine, and there was no evident difference about kidney indexes.④Compared with the model group, there was any improvement in every groups about pathological change. The effect of Yuehua capsules & western chemotherapy medicine group was the best among groups used medicine, and the next was the mid-dose group.
Conclusion:①Yuehua capsules could improve the important symptoms and disease indexes of rats with tuberculosis, and could reduce pathological damage of rats with tuberculosis.②The therapeutic effect of yuehua capsules mid-dose was the best in the three yuehua capsules groups.③The therapeutic effect of yuehua capsules & western medicine chemotherapy was better than that of groups that used only western medicine or yuehua capsules, and it was proved that yuehua capsules had a synergetic effect with western medicine.
方法：经尾静脉注射H37Bγ建立NIH小鼠感染结核杆菌模型。随机设立①正常组、②模型组、③月华胶囊低剂量组、④月华胶囊中剂量组、⑤月华胶囊高剂量组、⑥西药化疗(利福平+异烟肼+吡嗪酰胺)组,⑦月华胶囊联合西药化疗组。通过灌胃给药30天。观测：①主要症状改变：体温、体重、进食量；②致病指数：肺脏病变指数、脏器重量指数；③病理改变：肺、肝、脾、心、肾病理变化。
结果：模型组与正常组比较各项指标差异均有显著性差异。各组之间比较：①用药各组临床症状明显优于模型组(P<0.01,P<0.05),其中联合组效果最佳,与月华胶囊各组及西药组比较差异均有显著性意义(P<0.01,P<0.05),其与正常组比较差异无显著性；月华胶囊中剂量组优于高、低两个剂量组(P<0.01,P<0.05)。②用药各组肺脏病变指数均较模型组低(P＜0.01,P<0.05),且联合组优于单独用药各组(P<0.05),单独用药各组间比较差异无显著性意义。③各用药组胸腺与肺指数明显优于模型组(P<0.01,P<0.05),联合用药组较单独用药组效果更好(P<0.05)；用药各组肝、脾指数较模型组低,用药各组之间比较无显著差异；各组肾指数比较差异无统计学意义。④用药各组与模型组比较,病理损害均有不同程度的改善(P<0.01,P<0.05)；联合用药组效果最佳,中剂量组次之,与各组之间比较有显著性差异(P<0.01,P<0.05)。
结论：①月华胶囊能改善结核杆菌感染小鼠主要临床症状及致病指数,能显著降低结核杆菌对小鼠脏器的病理损害。②月华胶囊中剂量的效果最好。③月华胶囊与西药联合运用,效果优于单独用药组,说明两者间具有一定的协同作用。
Objective:Observe①the effect of yuehua capsules on important symptoms such as body temperature, weight and repast of rats with tuberculosis.②the effect of yuehua capsules on disease indexes of important organs of rats with tuberculosis.③the effect of yuehua capsules on pathomorphological change of rats with tuberculosis.
Methods:The NIH rats models infected tuberculosis were established by injecting H37RV into the tail vein of rats, which were grouped into the model group, western chemotherapy medicine (INH+RFP+PIA) group, Yuehua capsules high-dose group, Yuehua capsule mid-dose group, Yuehua capsule lower-dose group, Yuehua capsules & western chemotherapy medicine group, and the normal group was made before the models were built. The rats were fed by way of gavage with corresponding medicine or distilled water for 30 days continuously. The following targets were observed:①the change of important symptoms such as body temperature, body weight and food-intake.②the disease indexes such as lesion index of lung and weight index of visceral organs.③the pathomorphological change of important visceral organs such as lung, liver, spleen, kidney and heart.
Results:Compared with the normal group, all targets of the model group had evident difference (P<0.01,P<0.05). Compared with every group, groups that used medicine were better than the model group(P<0.01,P<0.05), especially yuehua capsules & western chemotherapy medicine group was best among them, and compared with the normal group, there was no evident difference, but in three yuehua capsules groups, the mid-dose group was best among them(P<0.05).②Compared with the model group, the lung disease indexes of every group was lower than that of it(P<0.01,P<0.05), and the Yuehua capsules & western medicine group was better than that of groups used single medicine, in which there was no difference obviously.③Compared with the model group, the disease indexes of thymus and lung of else every group were superior to that of the model group(P<0.05),and combined group was better than that of the western medicine group or yuehua capsules groups(P<0. 05).and there was no significant difference between combined group and the model group. Compared with model group, the indexes of liver and spleen of all groups were lower than that of the model group, but there was no evident difference among groups used medicine, and there was no evident difference about kidney indexes.④Compared with the model group, there was any improvement in every groups about pathological change. The effect of Yuehua capsules & western chemotherapy medicine group was the best among groups used medicine, and the next was the mid-dose group.
Conclusion:①Yuehua capsules could improve the important symptoms and disease indexes of rats with tuberculosis, and could reduce pathological damage of rats with tuberculosis.②The therapeutic effect of yuehua capsules mid-dose was the best in the three yuehua capsules groups.③The therapeutic effect of yuehua capsules & western medicine chemotherapy was better than that of groups that used only western medicine or yuehua capsules, and it was proved that yuehua capsules had a synergetic effect with western medicine.
引文
1. Raviglione, MC, Pio A. Evolution of WHO policies for tuberculosis control 1948-2001. Lancet,2002359 (9308):-775-780
2.张立兴.中国结核病控制工作面临的挑战[J].中华流行病学杂志2004；25(8)：-645
3.曾正国主编.现代实用结核病学[M]北京：科学技术文献出版社2003；2-13-14
4.肺结核居传染病发病数及死亡数首位[J].中国卫生质量管理2005；12(4)：-76
5.中国防痨协会.结核病诊断细菌学检验规程[j].中国防痨杂志1996；18(1)：-28-31
6.陈虹,罗永艾,周波.实验性糖尿病结核动物模型的建立[J].中国防痨杂志2002：24(8)-192-194
7.徐善荪.月华丸加减治疗肺结核咯血54例疗效观察[J].工企医刊1997；10(1)：-59-59
8.王花端.月华丸为主治疗复治性肺结核100例[J].中医研究1999；10(6)：-37
9.梁秋,李师.中西医结合治疗耐多药结核病的探讨[J].辽宁中医杂志2003；30(3)：-221-222
10.李鲁铭.中药月华丸对预防抗痨药引起的药物性肝炎的影响[J].中国中西医结合杂
志,2003；23(3)：-233-234
11.张联科,杨会芹.月华丸化裁治疗肺结核咯血49例观察[J].现代中医药2004；000(003)：-26-26
12.郑玲,郑珠玉,李光磊.中西医结合治疗肺阴亏耗型肺结核60例[J].福建中医药2005，36(1).-45-46
13.欧阳建军,伍参荣,白宇乾.月华胶囊对耐多药结核分枝杆菌抑菌效力的体外研究[J].湖南中医学院学报2003；23(5)：-14-15,
14.曾正国主编.现代实用结核病学[M]北京：科学技术文献出版社2003.2-5-6
15.刘文,胡巍.结核分枝杆菌的免疫机制及抗原研究进展[J].淄博学院学报2002；4(3)：-85
16.曾正国主编.现代实用结核病学[M]北京：科学技术文献出版社2003.2-18-20
17.端木宏谨.我国结核病控制工作现状及展望[J].中华结核和呼吸杂志1999；22(10)：-384
18.Tahaoglu k, Atac Q Sevim T, et al. The management of anti-tuberculosis drug-induced hepatotoxicity.Int J Tuberc Lung Dis2001;5(1):-65-69.
19 Saigal S,Agarwal SR,Nandeesh HP,et al,Safety of an ofloxacin-based antituberular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease:a preliminary report. J Gastroenterol Hepatol 2001;16(9):-1028-1032
20.彭卫生主编.新编结核病学.中国医药科技出版社[M].北京：1994：183：434：47
21.Stanford TJ,et al.Immunotherapy with mycobacterum vaccae as an adjunct to chemotherapy in the treatment of pulmonary Tuberculosis.Tubercle1990;71(1):87
22.李定越,卢润生等.结核病实验动物模型[J].四川医学2003；24(7)：-761
23李甘地主编.病理学.北京：人民卫生出版社.2003.(7)：-435
24.李定越,卢润生等.结核病实验动物模型[J].四川医学2003；2《(7)：-761
25.胡一江,李辉,刘海燕等.三种不同品种小鼠主要器官重量及长度的比较[J].中国实验动物学杂志1997；7(2)：-100-101
26.李吉庆,杨晓等.不同日龄Smad3基因剔除小鼠的脏器重量及脏器指数[J].实验动物科学与 管2003；20(1)：-11-13
27.李定越,卢润生等.结核病实验动物模型[J].四川医学2003；24(7)：-761
28.张立群,马伟路.结核病小鼠病理学与TH1／TH2细胞动力学及iNOS表达关系的研究[J].中华微生物学和免疫学杂志2001：21(2)：-166-170
29.翟文治,王亚章等.肺结核患者微循环障碍的临床研究[J].中华结核和呼吸杂志1997；20(1)：-60
30.张志仁,徐顺清,陈恙飞.硫酸锌对利福平致肝损伤的预防作用[J].中国药理学与毒理学杂志2000；14(3)：-222-251
31.Malcolm A, Steele MD. Toxic hepatitis with isoniazid and rifampin-a meta-analysis[J]. Chest,1999;2:465-471.
32.李甘地主编.病理学[M].北京：人民卫生出版社.2003.7-434-435
33.彭卫生,王英年等主编.新编结核病学[M3第1版.北京：中国医药科技出息社1994,85-93
34.Orozco LC. Distribution Of liposomes in tuberculous mice. Tubercle (London),1990, 71(3):-209
35.漆浩珊,卢润生等.不同毒力菌株与感染途径在树造结核动物模型中的作用[J].四川医学1997；18(3)：-151
36.杨奇,卢润生.结核病心脏病变的实验研究[J].中国防痨杂志1998；20(2)：-84
37.展昭民(未查到)等.砂仁麦冬汤对抗维甲酸副作用.中医杂志.1992,33(8)：-403
38.季光,刘平.扶正化瘀方药物血清对原代培养大鼠肝细胞增殖及胶原生成率的影响[J].中国实验方剂学杂志1997；3(2)：-22
39.周金黄主编.中药免疫药理学[M].北京：人民军医出版社,1994.-1124
2.张立兴.中国结核病控制工作面临的挑战[J].中华流行病学杂志2004；25(8)：-645
3.曾正国主编.现代实用结核病学[M]北京：科学技术文献出版社2003；2-13-14
4.肺结核居传染病发病数及死亡数首位[J].中国卫生质量管理2005；12(4)：-76
5.中国防痨协会.结核病诊断细菌学检验规程[j].中国防痨杂志1996；18(1)：-28-31
6.陈虹,罗永艾,周波.实验性糖尿病结核动物模型的建立[J].中国防痨杂志2002：24(8)-192-194
7.徐善荪.月华丸加减治疗肺结核咯血54例疗效观察[J].工企医刊1997；10(1)：-59-59
8.王花端.月华丸为主治疗复治性肺结核100例[J].中医研究1999；10(6)：-37
9.梁秋,李师.中西医结合治疗耐多药结核病的探讨[J].辽宁中医杂志2003；30(3)：-221-222
10.李鲁铭.中药月华丸对预防抗痨药引起的药物性肝炎的影响[J].中国中西医结合杂
志,2003；23(3)：-233-234
11.张联科,杨会芹.月华丸化裁治疗肺结核咯血49例观察[J].现代中医药2004；000(003)：-26-26
12.郑玲,郑珠玉,李光磊.中西医结合治疗肺阴亏耗型肺结核60例[J].福建中医药2005，36(1).-45-46
13.欧阳建军,伍参荣,白宇乾.月华胶囊对耐多药结核分枝杆菌抑菌效力的体外研究[J].湖南中医学院学报2003；23(5)：-14-15,
14.曾正国主编.现代实用结核病学[M]北京：科学技术文献出版社2003.2-5-6
15.刘文,胡巍.结核分枝杆菌的免疫机制及抗原研究进展[J].淄博学院学报2002；4(3)：-85
16.曾正国主编.现代实用结核病学[M]北京：科学技术文献出版社2003.2-18-20
17.端木宏谨.我国结核病控制工作现状及展望[J].中华结核和呼吸杂志1999；22(10)：-384
18.Tahaoglu k, Atac Q Sevim T, et al. The management of anti-tuberculosis drug-induced hepatotoxicity.Int J Tuberc Lung Dis2001;5(1):-65-69.
19 Saigal S,Agarwal SR,Nandeesh HP,et al,Safety of an ofloxacin-based antituberular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease:a preliminary report. J Gastroenterol Hepatol 2001;16(9):-1028-1032
20.彭卫生主编.新编结核病学.中国医药科技出版社[M].北京：1994：183：434：47
21.Stanford TJ,et al.Immunotherapy with mycobacterum vaccae as an adjunct to chemotherapy in the treatment of pulmonary Tuberculosis.Tubercle1990;71(1):87
22.李定越,卢润生等.结核病实验动物模型[J].四川医学2003；24(7)：-761
23李甘地主编.病理学.北京：人民卫生出版社.2003.(7)：-435
24.李定越,卢润生等.结核病实验动物模型[J].四川医学2003；2《(7)：-761
25.胡一江,李辉,刘海燕等.三种不同品种小鼠主要器官重量及长度的比较[J].中国实验动物学杂志1997；7(2)：-100-101
26.李吉庆,杨晓等.不同日龄Smad3基因剔除小鼠的脏器重量及脏器指数[J].实验动物科学与 管2003；20(1)：-11-13
27.李定越,卢润生等.结核病实验动物模型[J].四川医学2003；24(7)：-761
28.张立群,马伟路.结核病小鼠病理学与TH1／TH2细胞动力学及iNOS表达关系的研究[J].中华微生物学和免疫学杂志2001：21(2)：-166-170
29.翟文治,王亚章等.肺结核患者微循环障碍的临床研究[J].中华结核和呼吸杂志1997；20(1)：-60
30.张志仁,徐顺清,陈恙飞.硫酸锌对利福平致肝损伤的预防作用[J].中国药理学与毒理学杂志2000；14(3)：-222-251
31.Malcolm A, Steele MD. Toxic hepatitis with isoniazid and rifampin-a meta-analysis[J]. Chest,1999;2:465-471.
32.李甘地主编.病理学[M].北京：人民卫生出版社.2003.7-434-435
33.彭卫生,王英年等主编.新编结核病学[M3第1版.北京：中国医药科技出息社1994,85-93
34.Orozco LC. Distribution Of liposomes in tuberculous mice. Tubercle (London),1990, 71(3):-209
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