中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2009年
6期
450-455
,共6页
李伟%徐桂清%韩玉谦%郝二军%薛长湖
李偉%徐桂清%韓玉謙%郝二軍%薛長湖
리위%서계청%한옥겸%학이군%설장호
硫普罗宁钠%硫普罗宁%D-氨基半乳糖%急性肝损伤
硫普囉寧鈉%硫普囉寧%D-氨基半乳糖%急性肝損傷
류보라저납%류보라저%D-안기반유당%급성간손상
N-(2-mercaptopropionyl)-glycine sodium%tiopronin%D-galactosamine%acute liver injury
目的 观察并比较硫普罗宁钠(MPG-Na)及硫普罗宁(MPG)对急性肝损伤的预防和治疗作用.方法 采用D-氨基半乳糖(Gal) (800 mg·kg~(-1),ip) 制备小鼠急性肝损伤模型.预防性给药时,分别ip给予小鼠MPG-Na或MPG 37.5,75和150 mg·kg~(-1),共7 d,于最后一次给药后30 min,用Gal染毒造模.治疗性给药时,在Gal染毒造模30 min后分别 ip MPG-Na或MPG 37.5,75和150 mg·kg~(-1),共2 d.预防性给药小鼠Gal染毒24 h、治疗性给药小鼠染毒48 h后,检测血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、 总蛋白(TP)、白蛋白(Alb)和Alb/球蛋白比值(A/G).取肝脏组织,常规石蜡包埋,切片,HE染色,光镜下观察肝脏组织病理变化.结果 与正常对照组比较,模型组小鼠血清GPT和GOT活性明显升高,肝脏组织出现明显的脂肪变性、肿胀或肝细胞变性坏死.预防性给予MPG-Na 150 mg·kg~(-1)小鼠血清GPT和GOT活性与模型组比较显著降低,治疗性给予MPG-Na 3个剂量血清GPT活性与模型组比较均明显降低,TP, Alb和A/G比值均无明显变化.预防性和治疗性给药后,肝脏组织病理损伤均明显减轻.另外,预防性和治疗性给药2种条件下,MPG-Na的作用与MPG相当.结论 MPG-Na对Gal引起的急性肝损伤具有预防和治疗作用,与MPG作用相当.
目的 觀察併比較硫普囉寧鈉(MPG-Na)及硫普囉寧(MPG)對急性肝損傷的預防和治療作用.方法 採用D-氨基半乳糖(Gal) (800 mg·kg~(-1),ip) 製備小鼠急性肝損傷模型.預防性給藥時,分彆ip給予小鼠MPG-Na或MPG 37.5,75和150 mg·kg~(-1),共7 d,于最後一次給藥後30 min,用Gal染毒造模.治療性給藥時,在Gal染毒造模30 min後分彆 ip MPG-Na或MPG 37.5,75和150 mg·kg~(-1),共2 d.預防性給藥小鼠Gal染毒24 h、治療性給藥小鼠染毒48 h後,檢測血清穀丙轉氨酶(GPT)、穀草轉氨酶(GOT)、 總蛋白(TP)、白蛋白(Alb)和Alb/毬蛋白比值(A/G).取肝髒組織,常規石蠟包埋,切片,HE染色,光鏡下觀察肝髒組織病理變化.結果 與正常對照組比較,模型組小鼠血清GPT和GOT活性明顯升高,肝髒組織齣現明顯的脂肪變性、腫脹或肝細胞變性壞死.預防性給予MPG-Na 150 mg·kg~(-1)小鼠血清GPT和GOT活性與模型組比較顯著降低,治療性給予MPG-Na 3箇劑量血清GPT活性與模型組比較均明顯降低,TP, Alb和A/G比值均無明顯變化.預防性和治療性給藥後,肝髒組織病理損傷均明顯減輕.另外,預防性和治療性給藥2種條件下,MPG-Na的作用與MPG相噹.結論 MPG-Na對Gal引起的急性肝損傷具有預防和治療作用,與MPG作用相噹.
목적 관찰병비교류보라저납(MPG-Na)급류보라저(MPG)대급성간손상적예방화치료작용.방법 채용D-안기반유당(Gal) (800 mg·kg~(-1),ip) 제비소서급성간손상모형.예방성급약시,분별ip급여소서MPG-Na혹MPG 37.5,75화150 mg·kg~(-1),공7 d,우최후일차급약후30 min,용Gal염독조모.치료성급약시,재Gal염독조모30 min후분별 ip MPG-Na혹MPG 37.5,75화150 mg·kg~(-1),공2 d.예방성급약소서Gal염독24 h、치료성급약소서염독48 h후,검측혈청곡병전안매(GPT)、곡초전안매(GOT)、 총단백(TP)、백단백(Alb)화Alb/구단백비치(A/G).취간장조직,상규석사포매,절편,HE염색,광경하관찰간장조직병리변화.결과 여정상대조조비교,모형조소서혈청GPT화GOT활성명현승고,간장조직출현명현적지방변성、종창혹간세포변성배사.예방성급여MPG-Na 150 mg·kg~(-1)소서혈청GPT화GOT활성여모형조비교현저강저,치료성급여MPG-Na 3개제량혈청GPT활성여모형조비교균명현강저,TP, Alb화A/G비치균무명현변화.예방성화치료성급약후,간장조직병리손상균명현감경.령외,예방성화치료성급약2충조건하,MPG-Na적작용여MPG상당.결론 MPG-Na대Gal인기적급성간손상구유예방화치료작용,여MPG작용상당.
AIM To evaluate the prevention and treatment of N-(2-mercaptopropionyl)-glycine sodium (MPG-Na) and tiopronin (MPG) on acute liver injury. METHODS The experimental mouse model of hepatotoxicity induced by D-galactosamine (Gal) was applied to investigate preventive and remedial effects. In the preventive experiment, the mice were ip administered with MPG-Na or MPG 37.5，75 and 150 mg·kg~(-1), respectively, for 7 d. Gal 800 mg·kg~(-1) was ip given into the mice 30 min after the last administration. In the remedial experiment, the mice were ip given Gal 800 mg·kg~(-1) and 30 min later followed by MPG-Na or MPG 37.5, 75 and 150 mg·kg~(-1) , respectively, for 2 d. The mice were euthanized and serum was prepared 24 h (pre-treatment) or 48 h (post-treatment) after Gal injection. The activities of serum glutamyl pyruvic transaminase (GPT) and glutamyl oxaloacetic transaminase (GOT), the contents of total protein (TP) and albumin (Alb), and the Alb/globulin (A/G) ratio were determined. The liver tissues were collected for histopathological assessment (HE staining) under light microscope. RESULTS Compared with normal control group, the activities of serum GPT and GOT in model group were significantly increased. The injuries such as fatty degeneration and liver cell necrosis were observed. Compared with model group, the activities of GPT and GOT in pre-treatment groups were obviously decreased in MPG-Na 150 mg·kg~(-1) group. In post-treatment groups, the activity of GPT decreased in 3 MPG-Na groups. The contents of TP, Alb and A/G ratio had little change. In addition, MPG-Na alleviated the injuries such as fatty degeneration and liver cell necrosis obviously. Compared with MPG, MPG-Na showed similar effect. CONCLUSION MPG-Na has an obvious protective effect against Gal-induced acute liver injury in mice and the efficiency is equivalent as MPG.
