药物不良反应杂志
藥物不良反應雜誌
약물불량반응잡지
ADVERSE DRUG REACTIONS JOURNAL
2014年
6期
345-349
,共5页
孙向菊%吴玉波%蒋爱华%徐娜%梁晶%吴禹蒙
孫嚮菊%吳玉波%蔣愛華%徐娜%樑晶%吳禹矇
손향국%오옥파%장애화%서나%량정%오우몽
环磷酰胺%谷胱甘肽%磷脂酰胆碱类%药物性肝损伤
環燐酰胺%穀胱甘肽%燐脂酰膽堿類%藥物性肝損傷
배린선알%곡광감태%린지선담감류%약물성간손상
Cyclophosphamide%Glutathione%Phosphatidylcholines%Drug-induced liver injury
目的:分析比较还原型谷胱甘肽与多烯磷脂酰胆碱对环磷酰胺诱导小鼠肝损伤的防护作用。方法采用简单随机抽样法将40只昆明小鼠分为肝损伤模型组、还原型谷胱甘肽组、多烯磷脂酰胆碱组和对照组,每组10只。前3组小鼠实验第1~4天均腹腔注射环磷酰胺(100 mg· kg-1·d-1)诱导肝损伤,第5~14天分别腹腔注射0.9%氯化钠注射液0.2 ml、还原型谷胱甘肽180 mg · kg-1· d-1、多烯磷脂酰胆碱90 mg·kg-1·d-1;对照组同期腹腔注射等体积0.9%氯化钠注射液。实验第1天给药前和第15天测定小鼠体重;实验第15天,小鼠处死前眼眶取血测定血清总胆红素和谷胱甘肽水平,处死小鼠后取肝脏称重并计算肝脏系数,取肝组织测定丙氨酸转氨酶( ALT)、天冬氨酸转氨酶(AST)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)水平,并进行肝组织形态学观察。结果实验第15天,应用环磷酰胺的3组小鼠体重均明显低于对照组(P <0.01或 P <0.05),但还原型谷胱甘肽组体重高于肝损伤模型组(P <0.05);肝损伤模型组小鼠肝脏系数(5.74%±0.11%)高于对照组(4.68%±0.37%)和还原型谷胱甘肽组(4.81%±0.19%)(均 P <0.01),多烯磷脂酰胆碱组小鼠肝脏系数(5.25%±0.35%)]也高于对照组(P <0.05)。肝损伤模型组、还原型谷胱甘肽组、多烯磷脂酰胆碱组血清总胆红素水平[(129.8±1.9)、(110.9±1.3)、(125.7±2.6)μmol/ L]均高于对照组(100.8±3.0)μmol/ L(均 P <0.01),但还原型谷胱甘肽组低于肝损伤模型组(P <0.01)。肝损伤模型组和多烯磷脂酰胆碱组血清谷胱甘肽水平[(50.5±1.9)、(55.9±2.4)g/ L]均低于对照组和还原型谷胱甘肽组[(73.8±4.3)、(71.3±3.7)g/ L](均 P <0.01)。肝损伤模型组、还原型谷胱甘肽组、多烯磷脂酰胆碱组肝组织 AST、ALT、SOD 和 CAT 活性均低于对照组[(144.5±7.9)、(223.1±15.1)、(173.9±5.3)U/ mg 比(332.6±7.3)U/ mg],[(50.5±4.0)、(108.0±8.0)、(62.3±2.0)U/ mg 比(139.6±7.0)U/ mg],[(99.0±9.7)、(165.0±114.6)、(115.6±7.3)U/ mg 比(207.6±8.3)U/ mg],[(35.4±1.0)、(39.3±1.1)、(36.3±1.2)U/ mg比(42.5±2.3)U/ mg](均 P <0.01);MDA 水平均高于对照组[(23.4±2.6)、(16.3±1.5)、(20.2±1.9)nmol/ mg 比(10.2±2.2)nmol/ mg](均 P <0.01),但还原型谷胱甘肽组4种酶活性均高于多烯磷脂酰胆碱组和肝损伤模型组(P <0.01或 P <0.05),MDA 水平低于多烯磷脂酰胆碱组和肝损伤模型组(均 P <0.05)。肝损伤模型组小鼠肝组织出现大量小坏死灶,肝细胞结构不清晰,细胞间隙增大,有大量炎性反应细胞浸润;还原型谷胱甘肽组出现少量小坏死灶,大部分肝细胞结构正常;多烯磷脂酰胆碱组部分肝细胞出现间隙增大、肿胀和小坏死灶。结论还原型谷胱甘肽对环磷酰胺诱导小鼠肝损伤有明显的防护作用,多烯磷脂酰胆碱仅能提高环磷酰胺诱导肝损伤小鼠模型 ALT 活性。
目的:分析比較還原型穀胱甘肽與多烯燐脂酰膽堿對環燐酰胺誘導小鼠肝損傷的防護作用。方法採用簡單隨機抽樣法將40隻昆明小鼠分為肝損傷模型組、還原型穀胱甘肽組、多烯燐脂酰膽堿組和對照組,每組10隻。前3組小鼠實驗第1~4天均腹腔註射環燐酰胺(100 mg· kg-1·d-1)誘導肝損傷,第5~14天分彆腹腔註射0.9%氯化鈉註射液0.2 ml、還原型穀胱甘肽180 mg · kg-1· d-1、多烯燐脂酰膽堿90 mg·kg-1·d-1;對照組同期腹腔註射等體積0.9%氯化鈉註射液。實驗第1天給藥前和第15天測定小鼠體重;實驗第15天,小鼠處死前眼眶取血測定血清總膽紅素和穀胱甘肽水平,處死小鼠後取肝髒稱重併計算肝髒繫數,取肝組織測定丙氨痠轉氨酶( ALT)、天鼕氨痠轉氨酶(AST)、超氧化物歧化酶(SOD)、過氧化氫酶(CAT)活性和丙二醛(MDA)水平,併進行肝組織形態學觀察。結果實驗第15天,應用環燐酰胺的3組小鼠體重均明顯低于對照組(P <0.01或 P <0.05),但還原型穀胱甘肽組體重高于肝損傷模型組(P <0.05);肝損傷模型組小鼠肝髒繫數(5.74%±0.11%)高于對照組(4.68%±0.37%)和還原型穀胱甘肽組(4.81%±0.19%)(均 P <0.01),多烯燐脂酰膽堿組小鼠肝髒繫數(5.25%±0.35%)]也高于對照組(P <0.05)。肝損傷模型組、還原型穀胱甘肽組、多烯燐脂酰膽堿組血清總膽紅素水平[(129.8±1.9)、(110.9±1.3)、(125.7±2.6)μmol/ L]均高于對照組(100.8±3.0)μmol/ L(均 P <0.01),但還原型穀胱甘肽組低于肝損傷模型組(P <0.01)。肝損傷模型組和多烯燐脂酰膽堿組血清穀胱甘肽水平[(50.5±1.9)、(55.9±2.4)g/ L]均低于對照組和還原型穀胱甘肽組[(73.8±4.3)、(71.3±3.7)g/ L](均 P <0.01)。肝損傷模型組、還原型穀胱甘肽組、多烯燐脂酰膽堿組肝組織 AST、ALT、SOD 和 CAT 活性均低于對照組[(144.5±7.9)、(223.1±15.1)、(173.9±5.3)U/ mg 比(332.6±7.3)U/ mg],[(50.5±4.0)、(108.0±8.0)、(62.3±2.0)U/ mg 比(139.6±7.0)U/ mg],[(99.0±9.7)、(165.0±114.6)、(115.6±7.3)U/ mg 比(207.6±8.3)U/ mg],[(35.4±1.0)、(39.3±1.1)、(36.3±1.2)U/ mg比(42.5±2.3)U/ mg](均 P <0.01);MDA 水平均高于對照組[(23.4±2.6)、(16.3±1.5)、(20.2±1.9)nmol/ mg 比(10.2±2.2)nmol/ mg](均 P <0.01),但還原型穀胱甘肽組4種酶活性均高于多烯燐脂酰膽堿組和肝損傷模型組(P <0.01或 P <0.05),MDA 水平低于多烯燐脂酰膽堿組和肝損傷模型組(均 P <0.05)。肝損傷模型組小鼠肝組織齣現大量小壞死竈,肝細胞結構不清晰,細胞間隙增大,有大量炎性反應細胞浸潤;還原型穀胱甘肽組齣現少量小壞死竈,大部分肝細胞結構正常;多烯燐脂酰膽堿組部分肝細胞齣現間隙增大、腫脹和小壞死竈。結論還原型穀胱甘肽對環燐酰胺誘導小鼠肝損傷有明顯的防護作用,多烯燐脂酰膽堿僅能提高環燐酰胺誘導肝損傷小鼠模型 ALT 活性。
목적:분석비교환원형곡광감태여다희린지선담감대배린선알유도소서간손상적방호작용。방법채용간단수궤추양법장40지곤명소서분위간손상모형조、환원형곡광감태조、다희린지선담감조화대조조,매조10지。전3조소서실험제1~4천균복강주사배린선알(100 mg· kg-1·d-1)유도간손상,제5~14천분별복강주사0.9%록화납주사액0.2 ml、환원형곡광감태180 mg · kg-1· d-1、다희린지선담감90 mg·kg-1·d-1;대조조동기복강주사등체적0.9%록화납주사액。실험제1천급약전화제15천측정소서체중;실험제15천,소서처사전안광취혈측정혈청총담홍소화곡광감태수평,처사소서후취간장칭중병계산간장계수,취간조직측정병안산전안매( ALT)、천동안산전안매(AST)、초양화물기화매(SOD)、과양화경매(CAT)활성화병이철(MDA)수평,병진행간조직형태학관찰。결과실험제15천,응용배린선알적3조소서체중균명현저우대조조(P <0.01혹 P <0.05),단환원형곡광감태조체중고우간손상모형조(P <0.05);간손상모형조소서간장계수(5.74%±0.11%)고우대조조(4.68%±0.37%)화환원형곡광감태조(4.81%±0.19%)(균 P <0.01),다희린지선담감조소서간장계수(5.25%±0.35%)]야고우대조조(P <0.05)。간손상모형조、환원형곡광감태조、다희린지선담감조혈청총담홍소수평[(129.8±1.9)、(110.9±1.3)、(125.7±2.6)μmol/ L]균고우대조조(100.8±3.0)μmol/ L(균 P <0.01),단환원형곡광감태조저우간손상모형조(P <0.01)。간손상모형조화다희린지선담감조혈청곡광감태수평[(50.5±1.9)、(55.9±2.4)g/ L]균저우대조조화환원형곡광감태조[(73.8±4.3)、(71.3±3.7)g/ L](균 P <0.01)。간손상모형조、환원형곡광감태조、다희린지선담감조간조직 AST、ALT、SOD 화 CAT 활성균저우대조조[(144.5±7.9)、(223.1±15.1)、(173.9±5.3)U/ mg 비(332.6±7.3)U/ mg],[(50.5±4.0)、(108.0±8.0)、(62.3±2.0)U/ mg 비(139.6±7.0)U/ mg],[(99.0±9.7)、(165.0±114.6)、(115.6±7.3)U/ mg 비(207.6±8.3)U/ mg],[(35.4±1.0)、(39.3±1.1)、(36.3±1.2)U/ mg비(42.5±2.3)U/ mg](균 P <0.01);MDA 수평균고우대조조[(23.4±2.6)、(16.3±1.5)、(20.2±1.9)nmol/ mg 비(10.2±2.2)nmol/ mg](균 P <0.01),단환원형곡광감태조4충매활성균고우다희린지선담감조화간손상모형조(P <0.01혹 P <0.05),MDA 수평저우다희린지선담감조화간손상모형조(균 P <0.05)。간손상모형조소서간조직출현대량소배사조,간세포결구불청석,세포간극증대,유대량염성반응세포침윤;환원형곡광감태조출현소량소배사조,대부분간세포결구정상;다희린지선담감조부분간세포출현간극증대、종창화소배사조。결론환원형곡광감태대배린선알유도소서간손상유명현적방호작용,다희린지선담감부능제고배린선알유도간손상소서모형 ALT 활성。
Objective To analyze and compare the prothetic effects of reduced glutathione and polyene phosphatidyl choline on liver injury evoked by cyclophosphamide in mice. Methods Forty Kunming mice were divided into the liver injury model group,the reduced glutathione group,the polyene phosphatidyl choline group,and the control group by simple random sampling. Each group comprised 10 mice. The mice in the fornamed 3 groups received intraperitoneal injection of cyclophosphamide(100 mg ·kg-1 ·d-1 )to evoke the liver injury on day 1 to 4 of the experiment and 0. 9% sodium chloride solution 0. 2 ml,reduced glutathione 180 mg· kg-1 · d-1 ,and polyene phosphatidyl choline 90 mg·kg-1 ·d-1 were given respectively in the 3 groups on day 5 to 14 of the experiment. The mice in the control group received intraperitoneal injection of same volume of 0. 9% sodium chloride solution on day 1 to 14 of experiment. The body weight of mice in the 4 groups were measured on the first day before intraperitoneal injection of cyclophosphamide and the fifteenth day of the experiment. The mice in the 4 groups were executed on the fifteenth day of the experiment. The blood samples were taken from eye pit before the mice were killed and the serum total bilirubin and glutathione levels were measured. Their liver tissue were taken and weighed, and the liver coefficient were calculated. The liver tissue were taken and the activities of alanine aminotransferase( ALT),aspartate aminotransferase( AST),superoxide dismutase( SOD),catalase (CAT)and the level of malonaldehyde( MDA)in the liver tissue were measured. The morphological changes in the liver tissue in the 4 groups were observed. Results On day 15 of experi-ment,the body weights in mice in the liver injury model group,the reduced glutathione group,and the polyene phosphatidyl choline group were lower significantly than those in the control group(P < 0. 01 or P < 0. 05). The body weights in mice in the reduced glutathione group were higher than those in the liver injury model group(P <0. 05). The liver coefficient in mice in the liver injury model group(5. 74% ± 0. 11% )was higher than that in the control group(4. 68% ± 0. 37% )and the reduced glutathione group(4. 81% ± 0. 19% )(all P <0. 01). The liver coefficient in mice in the polyene phosphatidyl choline group(5. 25% ± 0. 35% )was higher than that in the control group(P < 0. 05). The levels of serum total bilirubin in the liver injury model group,the reduced glutathione group,and the polyene phosphatidyl choline group[(129. 8 ± 1. 9), (110. 9 ±1. 3),and(125. 7 ±2. 6)μmol/ L]were higher than those in the control group[(100. 8 ± 3. 0)μmol/ L](all P < 0. 01). The level of serum total bilirubin in mice in the reduced glutathione group was lower than that in the liver injury model group(P < 0. 01). The levels of serum glutathione in mice in the liver injury model group and the polyene phosphatidyl choline group[(50. 5 ± 1. 9)and(55. 9 ± 2. 4)g/ L] were lower than those in the control group and the reduced glutathione group[(73. 8 ± 4. 3)and(71. 3 ± 3. 7)g/ L](all P < 0. 01). The activities of AST,ALT,SOD,and CAT in the liver tissue in mice in the liver injury model group,the reduced glutathione group,and the polyene phosphatidyl choline group were lower than those in the control group[(144. 5 ± 7. 9),(223. 1 ± 15. 1),(173. 9 ± 5. 3)U/ mg vs.(332. 6 ± 7. 3)U/ mg],[(50. 5 ± 4. 0),(108. 0 ± 8. 0),(62. 3 ± 2. 0)U/ mg vs.(139. 6 ± 7. 0)U/ mg],[(99. 0 ± 9. 7),(165. 0 ± 114. 6),(115. 6 ± 7. 3)U/ mg vs. (207. 6 ± 8. 3)U/ mg],[(35. 4 ± 1. 0),(39. 3 ± 1. 1),(36. 3 ± 1. 2)U/ mg vs.(42. 5 ± 2. 3)U/ mg](all P < 0. 01). The MDA levels in the liver injury model group,the reduced glutathione group,and the polyene phosphatidyl choline group were higher than those in the control group[(23. 4 ± 2. 6),(16. 3 ± 1. 5),(20. 2 ± 1. 9)nmol/ mg vs.(10. 2 ± 2. 2)nmol/mg](all P < 0. 01). But the levels of above-mentioned four enzymes in the reduced glutathione group were higher than those in the polyene phosphatidyl choline group and the liver injury model group(P < 0. 01 or P< 0. 05),the levels of MDA were lower than those in the polyene phosphatidyl choline and the liver injury model groups(all P < 0. 05). There were many necrotic foci and inflammatory corpuscles in hepatic tissue in mice in the liver injury model group,the structure of hepatocyte was inordinate. The structure of most hepatocytes in the reduced glutathione group was normal,only few necrotic foci were seen. Part of the hepatocytes in the polyene phosphatidyl choline group showed gap increase,swelling,and a few necrotic foci. Conclusions Reduced glutathione has significant repairing effects on liver injury in mice evoked by cyclophosphamide. Polyene phosphatidyl choline can only increase the ALT activity in the model of liver injury evoked by cyclophosphamide in mice.