国际医学寄生虫病杂志
國際醫學寄生蟲病雜誌
국제의학기생충병잡지
INTERNATIONAL JOURNAL OF MEDICAL PARASITIC DISEASES
2014年
5期
257-262
,共6页
血吸虫病%山奈酚%肝纤维化%α-平滑肌肌动蛋白%组织金属蛋白酶抑制因子%Ⅰ型胶原%Ⅲ型胶原
血吸蟲病%山奈酚%肝纖維化%α-平滑肌肌動蛋白%組織金屬蛋白酶抑製因子%Ⅰ型膠原%Ⅲ型膠原
혈흡충병%산내분%간섬유화%α-평활기기동단백%조직금속단백매억제인자%Ⅰ형효원%Ⅲ형효원
Schistosomiasis%Kaempferol%Hepatic fibrosis%α-smooth muscle actin%Tissue inhibitor of metalloproteinase%Type Ⅰ collagen%Type Ⅲ collagen
目的 研究感染日本血吸虫的小鼠经吡喹酮杀虫治疗后,给予山奈酚治疗对小鼠肝组织虫卵肉芽肿和纤维化的影响. 方法 以日本血吸虫尾蚴感染BALB/c小鼠作为肝纤维化动物模型,将40只健康BALB/c小鼠随机分为6组:正常组和模型组各8只,山奈酚组设5、10、15、20 mg/(kg·d)等4个剂量组,每组6只.除正常组外,其余5组小鼠感染日本血吸虫后6周给予吡喹酮灌胃治疗,剂量为500mg/(kg·d)×2 d.吡喹酮治疗后,山奈酚组小鼠分别给予山奈酚5、10、15、20 mg/(kg·d)灌胃治疗6周,正常组和模型组给予等体积生理盐水灌胃6周.治疗结束后颈椎脱臼处死小鼠,取肝脏.用免疫组织化学法检测各组小鼠肝组织金属蛋白酶抑制因子(tissue inhibitor of metalloproteinase,TIMP)1、α-平滑肌动蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型胶原(type Ⅰ collagen,COLⅠ)、Ⅲ型胶原(typeⅢcollagen,COLⅢ)蛋白的表达;用实时荧光定量RT-PCR检测各组小鼠肝组织α-SMA、TIMP1、COLⅢmRNA的表达. 结果 山奈酚20 mg/(kg·d)组小鼠肝组织α-SMA、TIMP1、COLⅢmRNA的表达量依次为:1.251 7±0.053 8、1.490 1±0.042 9、1.328 3±0.070 3.模型小鼠肝组织α-SMA、TIMP1、COLⅢmRNA的表达量依次为:2.141 7±0.038 6、4.281 7±0.089 1、5.218 3±0.121 6.与模型组相比,山奈酚各剂量组α-SMA、TIMP1、COLⅢ的mRNA的表达量降低,差异均有统计学意义(F=36.93、95.16、48.29,P＜0.05);山奈酚4个剂量组之间,随用药剂量增大,α-SMA、TIMP1、COLⅢmRNA的表达量下降,差异均有统计学意义(F=70.62、290.51、407.25,P＜0.05).与模型组相比,山奈酚各剂量组α-SMA、TIMP1、COL Ⅰ、COLⅢ蛋白表达量下降,差异有统计学意义(F=13.46、237.96、191.58、274.32,P＜0.05);山奈酚4个剂量组之间,随用药剂量增大,α-SMA、TIMP1、COLⅠ、COLⅢ蛋白表达量下降,差异有统计学意义(F=210.92、77.41、186.33、53.18,P＜0.05). 结论 山奈酚可通过减少α-SMA、TIMP1、COLⅠ、COLⅢ的表达,能显著减轻日本血吸虫引起的小鼠肝纤维化.
目的 研究感染日本血吸蟲的小鼠經吡喹酮殺蟲治療後,給予山奈酚治療對小鼠肝組織蟲卵肉芽腫和纖維化的影響. 方法 以日本血吸蟲尾蚴感染BALB/c小鼠作為肝纖維化動物模型,將40隻健康BALB/c小鼠隨機分為6組:正常組和模型組各8隻,山奈酚組設5、10、15、20 mg/(kg·d)等4箇劑量組,每組6隻.除正常組外,其餘5組小鼠感染日本血吸蟲後6週給予吡喹酮灌胃治療,劑量為500mg/(kg·d)×2 d.吡喹酮治療後,山奈酚組小鼠分彆給予山奈酚5、10、15、20 mg/(kg·d)灌胃治療6週,正常組和模型組給予等體積生理鹽水灌胃6週.治療結束後頸椎脫臼處死小鼠,取肝髒.用免疫組織化學法檢測各組小鼠肝組織金屬蛋白酶抑製因子(tissue inhibitor of metalloproteinase,TIMP)1、α-平滑肌動蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型膠原(type Ⅰ collagen,COLⅠ)、Ⅲ型膠原(typeⅢcollagen,COLⅢ)蛋白的錶達;用實時熒光定量RT-PCR檢測各組小鼠肝組織α-SMA、TIMP1、COLⅢmRNA的錶達. 結果 山奈酚20 mg/(kg·d)組小鼠肝組織α-SMA、TIMP1、COLⅢmRNA的錶達量依次為:1.251 7±0.053 8、1.490 1±0.042 9、1.328 3±0.070 3.模型小鼠肝組織α-SMA、TIMP1、COLⅢmRNA的錶達量依次為:2.141 7±0.038 6、4.281 7±0.089 1、5.218 3±0.121 6.與模型組相比,山奈酚各劑量組α-SMA、TIMP1、COLⅢ的mRNA的錶達量降低,差異均有統計學意義(F=36.93、95.16、48.29,P＜0.05);山奈酚4箇劑量組之間,隨用藥劑量增大,α-SMA、TIMP1、COLⅢmRNA的錶達量下降,差異均有統計學意義(F=70.62、290.51、407.25,P＜0.05).與模型組相比,山奈酚各劑量組α-SMA、TIMP1、COL Ⅰ、COLⅢ蛋白錶達量下降,差異有統計學意義(F=13.46、237.96、191.58、274.32,P＜0.05);山奈酚4箇劑量組之間,隨用藥劑量增大,α-SMA、TIMP1、COLⅠ、COLⅢ蛋白錶達量下降,差異有統計學意義(F=210.92、77.41、186.33、53.18,P＜0.05). 結論 山奈酚可通過減少α-SMA、TIMP1、COLⅠ、COLⅢ的錶達,能顯著減輕日本血吸蟲引起的小鼠肝纖維化.
목적 연구감염일본혈흡충적소서경필규동살충치료후,급여산내분치료대소서간조직충란육아종화섬유화적영향. 방법 이일본혈흡충미유감염BALB/c소서작위간섬유화동물모형,장40지건강BALB/c소서수궤분위6조:정상조화모형조각8지,산내분조설5、10、15、20 mg/(kg·d)등4개제량조,매조6지.제정상조외,기여5조소서감염일본혈흡충후6주급여필규동관위치료,제량위500mg/(kg·d)×2 d.필규동치료후,산내분조소서분별급여산내분5、10、15、20 mg/(kg·d)관위치료6주,정상조화모형조급여등체적생리염수관위6주.치료결속후경추탈구처사소서,취간장.용면역조직화학법검측각조소서간조직금속단백매억제인자(tissue inhibitor of metalloproteinase,TIMP)1、α-평활기동단백(α-smooth muscle actin,α-SMA)、Ⅰ형효원(type Ⅰ collagen,COLⅠ)、Ⅲ형효원(typeⅢcollagen,COLⅢ)단백적표체;용실시형광정량RT-PCR검측각조소서간조직α-SMA、TIMP1、COLⅢmRNA적표체. 결과 산내분20 mg/(kg·d)조소서간조직α-SMA、TIMP1、COLⅢmRNA적표체량의차위:1.251 7±0.053 8、1.490 1±0.042 9、1.328 3±0.070 3.모형소서간조직α-SMA、TIMP1、COLⅢmRNA적표체량의차위:2.141 7±0.038 6、4.281 7±0.089 1、5.218 3±0.121 6.여모형조상비,산내분각제량조α-SMA、TIMP1、COLⅢ적mRNA적표체량강저,차이균유통계학의의(F=36.93、95.16、48.29,P＜0.05);산내분4개제량조지간,수용약제량증대,α-SMA、TIMP1、COLⅢmRNA적표체량하강,차이균유통계학의의(F=70.62、290.51、407.25,P＜0.05).여모형조상비,산내분각제량조α-SMA、TIMP1、COL Ⅰ、COLⅢ단백표체량하강,차이유통계학의의(F=13.46、237.96、191.58、274.32,P＜0.05);산내분4개제량조지간,수용약제량증대,α-SMA、TIMP1、COLⅠ、COLⅢ단백표체량하강,차이유통계학의의(F=210.92、77.41、186.33、53.18,P＜0.05). 결론 산내분가통과감소α-SMA、TIMP1、COLⅠ、COLⅢ적표체,능현저감경일본혈흡충인기적소서간섬유화.
Objective To investigate the effect of kaempferol on periovular granuloma and liver fibrosis in mice with schistosomiasis japonicum after treatment with praziquantel.Methods BALB/c mice infected with schistosomiasis japonicum were used for animal model of liver fibrosis.Forty BALB/c mice were randomly divided into a normal group (8 mice),a model group (8 mice),and 4 kaempferol groups with different kaempferol dosages [5,10,15,20 mg/(kg·d) respectively,6 mice each group].Besides the normal group,all the mice in the other 5 groups were infected with Schistosoma japonicum,and 6 weeks after the infection,were treated with praziquantel 500 mg/(kg·d) for 2 d.Kaempferol groups were administered intragastrically with kaempferol 5,10,15,20 mg/(kg·d) respectively for 6 weeks.The mice in normal group and model group were administered with normal saline for 6 weeks.All mice were sacrificed at the end of treatment.The protein expression of tissue inhibitors of metalloproteinases(TIMP)1,α-smooth muscle actin(α-SMA),type Ⅰ collagen (COL Ⅰ),type Ⅲ collagen (COLⅢ) on tissue microarray sections was detected by immunohistochemistry.The levels of mRNA expression of hepatic α-SMA,TIMP1,CO Ⅲ,mRNA were determined by RT-PCR.Results The relative mRNA expression levels of α-SMA,TIMP1,COL Ⅲ in liver tissues of kaempferol 20 mg/(kg·d) group were 1.251 7±0.053 8,1.490 1±0.042 9 and 1.328 3±0.070 3.The relative mRNA expression levels of α-SMA,TIMP1,COLⅢ in liver tissues of modle group were 2.141 7±0.038 6,4.281 7±0.089 1 and 5.218 3± 0.121 6.The levels of mRNA expression of hepatic α-SMA,TIMP1,type Ⅲ collagen in kaempferol treated groups were lower than those in the modle group.There was significant difference among the five groups (F=36.93,95.16,48.29,P＜0.05).Increasing with the drug concentration of kaempferol,the mRNA expression levels of α-SMA,TIMP1,type Ⅲ collagen were significantly reduced in four dose groups,there was significant difference among the four groups (F=70.62,290.51,407.25,P＜0.05),and the protein expression levels of α-SMA,TIMP1,types Ⅰ and Ⅲ collagen were significantly reduced in four dose groups,there was significant difference among the four groups (F=210.92,77.41,186.33,53.18,P＜0.05).Conclusion By inhibiting the expressions of α-SMA,TIMP1,ypes Ⅰ and Ⅲ collagen,kaempferol can significantly reduce the degree of hepatic fibrosis caused by schistosome eggs.
