阿苯達唑殼聚糖微球抗小鼠泡球蚴藥效實驗研究
發(fā)布時間：2018-11-17 07:56
【摘要】：目的:通過比較阿苯達唑殼聚糖微球(Albendazole Chitosan Mi c r o s p h e r e s,A B Z-C S-M P s)與阿苯達唑脂質(zhì)體(Liposome-Albendazole,L-ABZ)、阿苯達唑片劑(Albendazole Tablet,ABZ-T)經(jīng)口灌注治療繼發(fā)性感染多房棘球蚴小鼠的效果,評價阿苯達唑殼聚糖微球抗小鼠泡球蚴病的藥效,為提高泡球蚴病藥物治療提供實驗依據(jù)。方法:雄性昆明小鼠2 2 0只,通過腹腔接種建立繼發(fā)性感染多房棘球蚴小鼠模型,接種1 2周后,將小鼠隨機分為4組:ABZ-CS-MPs治療組、L-ABZ治療組、ABZ-T治療組及模型對照組(另設空白對照組2 0只),其前三治療組按口服A B Z劑量分別為3 7.5 m g/k g、7 5.0 m g/k g、1 5 0.0 m g/k g為標準,又分成三個劑量組,每個劑量組2 0只小鼠,模型對照組給予0.2 m L生理鹽水。所有小鼠飼養(yǎng)1 2周后開始灌胃給藥,每周三次(每隔一天),連續(xù)治療1 2周后剖檢。用藥治療后評價藥效的指標如下:(1)觀察小鼠肝臟大體形態(tài);(2)稱量囊濕重并計算抑囊率;(3)病理組織學觀察;(4)電鏡觀察泡球蚴組織的超微結(jié)構(gòu)變化;(5)高效液相色譜法(H P L C)測定小鼠血漿及肝臟勻漿中阿苯達唑主要代謝產(chǎn)物阿苯達唑亞砜(a b l e n d a z o l e s u l f o x i d e,A B Z-S X)的濃度。結(jié)果:經(jīng)剖檢發(fā)現(xiàn),所有治療組泡球蚴組織跟模型對照組比較囊腫明顯縮小,其中A B ZC S-M P s治療組及L-ABZ治療組小鼠泡球蚴組織較ABZ-T治療組明顯萎縮及塌陷,大多數(shù)泡球蚴組織外觀呈黃色或乳白色、質(zhì)地變硬,實變或鈣化程度明顯。各治療組3 7.5 m g/k g,7 5 m g/k g,1 5 0 m g/k g劑量組泡球蚴囊濕重分別為:A B Z-C S-M P s:(0.1 7 6±0.0 3 3,0.1 2 3±0.0 1 6,0.0 8 5±0.0 2 9)g;L-A B Z:(0.1 5 6±0.0 2 0,0.1 4 7±0.0 2 6,0.1 3 7±0.0 2 6)g;A B Z-T:(0.4 9 6±0.0 9 5,0.4 3 3±0.0 6 9,0.3 3 7±0.0 6 3)g;與模型對照組(1.5 6 5±0.0 2 0)g比較差異均有統(tǒng)計學意義(P0.0 5)。各治療組7 5 m g/k g和1 5 0 m g/k g劑量組中A B Z-C SM P s組抑囊率分別達到9 2.1 3%,9 4.5 6%,其明顯高于L-A B Z(9 0.5 8%,9 1.2 3%)和A B ZT(7 2.3 2%,7 8.4 6%)。組織學觀察發(fā)現(xiàn),經(jīng)A B Z-C S-M P s或L-A B Z治療后泡球蚴組織有不同程度變形壞死,生發(fā)層和角質(zhì)層嚴重損害,典型泡球蚴結(jié)構(gòu)消失。同時,通過A B ZC S-M P s或L-A B Z治療后,血漿中A B Z-S X濃度達到較高水平,各用藥組3 7.5 m g/k g,7 5 m g/k g,1 5 0 m g/k g劑量組血漿A B Z-S X濃度分別為:A B Z-C S-M P s:(0.6 7 8 5,1.1 0 1 1,1.4 0 3 5)μg/m l;L-A B Z:(1.0 4 1 0,0.8 5 8 7,1.0 2 7 5)μg/m l;A B Z-T:(0.3 1 4 1,0.4 3 0 7,0.5 4 0 9)μg/m l;A B Z-C S-M P s治療組血漿A B Z-S X濃度在7 5 m g/k g以及1 5 0 m g/k g劑量組在各治療組中最高,與A B Z-T組比較差異有統(tǒng)計學意義(P0.0 1)。結(jié)論:三種ABZ劑型對小鼠泡球蚴生長均有不同程度的抑制作用,尤其是A B Z-C S-M P s有效地促進A B Z的經(jīng)腸吸收,可明顯提高阿苯達唑主要代謝產(chǎn)物阿苯達唑亞砜在血漿中的濃度,有望成為治療包蟲病的一種新的劑型。
[Abstract]:Objective: to compare albendazole chitosan microspheres (Albendazole Chitosan Mi c r o s p h e r e SSA B Z-C S-M P s) with albendazole liposome (Liposome-Albendazole,L-ABZ), albendazole tablet (Albendazole Tablet,) To evaluate the efficacy of albendazole chitosan microspheres in the treatment of alveolar echinococcosis in mice, and to provide experimental evidence for improving drug treatment of alveolar echinococcosis. Methods: 220 male Kunming mice were inoculated intraperitoneally to establish the mice model of secondary infection of echinococcus multilocularis. After 12 weeks of inoculation, mice were randomly divided into four groups: ABZ-CS-MPs group and L-ABZ group. ABZ-T treatment group and model control group (20 blank control group), the first three treatment groups according to the oral A B Z dose of 75.0 mg / kg of 150.0 mg / kg, as the standard. The mice were divided into three dose groups, 20 mice in each dose group, and 0.2 mL normal saline was given to the model control group. After 12 weeks of feeding, all mice were given intragastric administration, three times a week (every other day), after 12 weeks of continuous treatment. The indexes to evaluate the efficacy after treatment were as follows: (1) observing the gross morphology of the liver; (2) weighing the wet weight of the capsule and calculating the inhibition rate; (3) observing the histopathology; (4) observing the ultrastructural changes of the hydatid tissues by electron microscope; (5) the concentration of albendazole in plasma and liver homogenate of mice was determined by (H P L C). The main metabolite of albendazole sulfoxide (a b l e n d a z o l e s u l f o x i d B Z-S X was albendazole sulfoxide. Results: the results showed that the alveolar hydatid tissues in all treatment groups were significantly smaller than those in the model control group, and the alveolar hydatid tissues in the A B ZC S-M P s treatment group and the L-ABZ treatment group were significantly smaller and collapsed than those in the ABZ-T treatment group. The appearance of most alveolar hydatid tissues was yellow or milky white, the texture became hard, and the degree of consolidation or calcification was obvious. In each treatment group, 37.5 mg / k g / k g = 7.5 mg / k g / k g, 7 5 mg / k g / g, The wet weight of hydatid cyst in 150 mg / kg dose group was: A B Z-C S-M P s: (0.1 7 6 鹵0.033 鹵0.23 鹵0.016 鹵0.08 5 鹵0.029 g, respectively. L-A B Z: (was 0.41 鹵0.026 鹵0.026 鹵0.37 鹵0.026) GB Z-T: (0.49 6 鹵0.09 5) 0.43 鹵0.069 0.37 鹵0.063 g; There was significant difference between the model control group and the model control group (1.55 鹵0.20) g (P 0.05). The inhibitory rate of A B Z-C SM P s in the groups of 7.5 mg / kg and 150 mg / kg in each treatment group reached 9.2.1% 34.56%, which was significantly higher than that of L-A B Z (9.0.58%. A B ZT (7,2.32% and 7.8.46%). Histological observation showed that after treatment with A B Z-C S-M P s or L A B Z, alveolar hydatid tissues were deformed and necrotized to varying degrees, germinal layer and cuticle were seriously damaged, and typical alveolar hydatid structure disappeared. At the same time, after treatment with A B ZC S-M P s or L-A B Z, the plasma A B Z S X concentration reached a higher level. The concentration of plasma A B Z S X reached a higher level after treatment with A B ZC S-M P s or L A B Z. In 150 mg / kg group, the plasma A B Z S X concentration was: A B Z-C S-M P s: (0.6 7 8 5 1 01 1 1 1 0 3 5) 渭 g / ml; L-A B Z: (1.041 0 0 0 0.8 58 7 + 1.027 5) 渭 g / mL A Z T: (0 31 1 0. 4 3 0 7 0 7 0 5 0 09) 渭 g / m 1; The concentration of plasma A B Z S X in the A B Z C S M P s treatment group was the highest in each treatment group at the dose of 7.5 mg / kg and 150 mg / kg respectively, which was significantly different from that in the A B Z T group (P 0.01). Conclusion: all of the three ABZ formulations can inhibit the growth of mouse alveolar echinococci to varying degrees, especially A B Z-C S-M P s can effectively promote the intestinal absorption of A B Z. Albendazole sulfoxide, the main metabolite of albendazole, can significantly increase the concentration of albendazole sulfoxide in plasma and may become a new dosage form for the treatment of hydatid disease.
【學位授予單位】：石河子大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R532.32
本文編號：2337034
[Abstract]:Objective: to compare albendazole chitosan microspheres (Albendazole Chitosan Mi c r o s p h e r e SSA B Z-C S-M P s) with albendazole liposome (Liposome-Albendazole,L-ABZ), albendazole tablet (Albendazole Tablet,) To evaluate the efficacy of albendazole chitosan microspheres in the treatment of alveolar echinococcosis in mice, and to provide experimental evidence for improving drug treatment of alveolar echinococcosis. Methods: 220 male Kunming mice were inoculated intraperitoneally to establish the mice model of secondary infection of echinococcus multilocularis. After 12 weeks of inoculation, mice were randomly divided into four groups: ABZ-CS-MPs group and L-ABZ group. ABZ-T treatment group and model control group (20 blank control group), the first three treatment groups according to the oral A B Z dose of 75.0 mg / kg of 150.0 mg / kg, as the standard. The mice were divided into three dose groups, 20 mice in each dose group, and 0.2 mL normal saline was given to the model control group. After 12 weeks of feeding, all mice were given intragastric administration, three times a week (every other day), after 12 weeks of continuous treatment. The indexes to evaluate the efficacy after treatment were as follows: (1) observing the gross morphology of the liver; (2) weighing the wet weight of the capsule and calculating the inhibition rate; (3) observing the histopathology; (4) observing the ultrastructural changes of the hydatid tissues by electron microscope; (5) the concentration of albendazole in plasma and liver homogenate of mice was determined by (H P L C). The main metabolite of albendazole sulfoxide (a b l e n d a z o l e s u l f o x i d B Z-S X was albendazole sulfoxide. Results: the results showed that the alveolar hydatid tissues in all treatment groups were significantly smaller than those in the model control group, and the alveolar hydatid tissues in the A B ZC S-M P s treatment group and the L-ABZ treatment group were significantly smaller and collapsed than those in the ABZ-T treatment group. The appearance of most alveolar hydatid tissues was yellow or milky white, the texture became hard, and the degree of consolidation or calcification was obvious. In each treatment group, 37.5 mg / k g / k g = 7.5 mg / k g / k g, 7 5 mg / k g / g, The wet weight of hydatid cyst in 150 mg / kg dose group was: A B Z-C S-M P s: (0.1 7 6 鹵0.033 鹵0.23 鹵0.016 鹵0.08 5 鹵0.029 g, respectively. L-A B Z: (was 0.41 鹵0.026 鹵0.026 鹵0.37 鹵0.026) GB Z-T: (0.49 6 鹵0.09 5) 0.43 鹵0.069 0.37 鹵0.063 g; There was significant difference between the model control group and the model control group (1.55 鹵0.20) g (P 0.05). The inhibitory rate of A B Z-C SM P s in the groups of 7.5 mg / kg and 150 mg / kg in each treatment group reached 9.2.1% 34.56%, which was significantly higher than that of L-A B Z (9.0.58%. A B ZT (7,2.32% and 7.8.46%). Histological observation showed that after treatment with A B Z-C S-M P s or L A B Z, alveolar hydatid tissues were deformed and necrotized to varying degrees, germinal layer and cuticle were seriously damaged, and typical alveolar hydatid structure disappeared. At the same time, after treatment with A B ZC S-M P s or L-A B Z, the plasma A B Z S X concentration reached a higher level. The concentration of plasma A B Z S X reached a higher level after treatment with A B ZC S-M P s or L A B Z. In 150 mg / kg group, the plasma A B Z S X concentration was: A B Z-C S-M P s: (0.6 7 8 5 1 01 1 1 1 0 3 5) 渭 g / ml; L-A B Z: (1.041 0 0 0 0.8 58 7 + 1.027 5) 渭 g / mL A Z T: (0 31 1 0. 4 3 0 7 0 7 0 5 0 09) 渭 g / m 1; The concentration of plasma A B Z S X in the A B Z C S M P s treatment group was the highest in each treatment group at the dose of 7.5 mg / kg and 150 mg / kg respectively, which was significantly different from that in the A B Z T group (P 0.01). Conclusion: all of the three ABZ formulations can inhibit the growth of mouse alveolar echinococci to varying degrees, especially A B Z-C S-M P s can effectively promote the intestinal absorption of A B Z. Albendazole sulfoxide, the main metabolite of albendazole, can significantly increase the concentration of albendazole sulfoxide in plasma and may become a new dosage form for the treatment of hydatid disease.
【學位授予單位】：石河子大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R532.32
【參考文獻】
相關期刊論文 前10條
1 朱帝文;穆民;任偉新;胡漢華;湯朝安;溫浩;;經(jīng)門靜脈藥物灌注化療栓塞治療大鼠肝泡狀棘球蚴病的電鏡觀察[J];介入放射學雜志;2013年08期
2 邱加閩,SchantzPeter,王謙,何金戈,陳興旺,劉鳳潔;奧芬達唑(Oxfendazole)治療小鼠實驗性泡球蚴病效果初步觀察[J];實用寄生蟲病雜志;1999年03期
3 沙先誼,馬燕,張學農(nóng),方曉玲;阿苯達唑納米球大鼠體內(nèi)藥動學[J];中國藥學雜志;2005年16期
4 柴君杰,孟賀巴特,焦偉,孫德玉,梁斌,石勁草,付承,李雄,毛一丁,王秀玲,多力坤,古麗拜爾,王燕春,高芳華,肖樹華;阿苯達唑乳劑治療肝囊型包蟲病212例臨床療效觀察(英文)[J];Chinese Medical Journal;2002年12期
5 王建華,溫浩,孫殿甲;阿苯達唑的體內(nèi)過程和劑型研究進展[J];中國寄生蟲病防治雜志;2002年03期
6 張金輝,溫浩,欒梅香,柯山,苗玉清;阿苯達唑新劑型抗包蟲病的藥效學實驗研究[J];中國寄生蟲病防治雜志;2003年03期
7 張龍;張示杰;;泡狀棘球蚴在人宿主中的生存機制研究進展[J];中國病原生物學雜志;2010年09期
8 柴君杰,孟賀巴特,焦偉,孫德玉,梁斌,石勁草,付承,李雄,毛一丁,王秀玲,多力坤,古麗拜爾,王燕春,高芳華,肖樹華;阿苯達唑乳劑治療肝囊型包蟲病212例臨床療效觀察[J];中國寄生蟲學與寄生蟲病雜志;2001年03期
9 樊玉祥;任偉新;迪力木拉提·巴吾冬;顧俊鵬;許曉東;張海瀟;紀衛(wèi)政;姜濤;溫浩;;阿苯達唑微球肝動脈灌注對大鼠肝泡狀棘球蚴病的治療作用[J];中國寄生蟲學與寄生蟲病雜志;2011年06期
10 Giuseppe Nunnari;Marilia R Pinzone;Salvatore Gruttadauria;Benedetto M Celesia;Giordano Madeddu;Giulia Malaguarnera;Piero Pavone;Alessandro Cappellani;Bruno Cacopardo;;Hepatic echinococcosis:Clinical and therapeutic aspects[J];World Journal of Gastroenterology;2012年13期
，本文編號：2337034
本文鏈接：http://sikaile.net/yixuelunwen/chuanranbingxuelunwen/2337034.html
最近更新
教材專著
