癌变·畸变·突变
癌變·畸變·突變
암변·기변·돌변
CARCINOGENSES,TERATOGENSIS AND MUTAGENESIS
2014年
6期
459-462
,共4页
白屈菜红碱%大鼠%长期毒性%细胞毒性%刺激性
白屈菜紅堿%大鼠%長期毒性%細胞毒性%刺激性
백굴채홍감%대서%장기독성%세포독성%자격성
Chelidonium majus%rat%long-term toxicity%cell toxicity%irritation
目的：观察连续给予抗肿瘤药物白屈菜红碱对大鼠的长期毒性。方法：采用Wistar大鼠，(12.6、8.4、5.6和3.7 mg/kg)及溶剂对照组，每组20只。腹腔注射给药6 d，停药8 d为1个周期，连续给药3个周期，间歇给药结束后12.6 mg/kg剂量组解剖大鼠6只，8.4 mg/kg剂量组解剖大鼠8只，其余每组解剖大鼠12只，停药观察4周后解剖各组剩余大鼠，进行一般状况、体质量、饲料摄入量、血液学、血清生化学、尸体解剖和脏器系数以及病理组织学检查。结果：大鼠在给药后，12.6和8.4 mg/kg剂量组立即出现腹膜刺激征，一周之内出现消瘦和被动体态等，体质量增长缓慢，摄食量减少，甚至死亡。与对照组比较，白屈菜红碱5.6 mg/kg以上剂量组大鼠红细胞系各项指标降低，白细胞数及白细胞分类异常，凝血时间延长，葡萄糖降低，碱性磷酸酶增加(P<0.05或<0.01)；并可观察到肺脏瘀血，腹腔大量血性腹水，脏器粘连并严重变形，肝脏和脾脏明显增大，前列腺和睾丸系数明显减小(P<0.05或P<0.01)，睾丸生精上皮细胞和精子明显损伤等。结论：白屈菜红碱在≥5.6 mg/kg剂量下，可引起大鼠局部刺激和药物毒性所引起的全身性异常反应，以致部分大鼠死亡。
目的：觀察連續給予抗腫瘤藥物白屈菜紅堿對大鼠的長期毒性。方法：採用Wistar大鼠，(12.6、8.4、5.6和3.7 mg/kg)及溶劑對照組，每組20隻。腹腔註射給藥6 d，停藥8 d為1箇週期，連續給藥3箇週期，間歇給藥結束後12.6 mg/kg劑量組解剖大鼠6隻，8.4 mg/kg劑量組解剖大鼠8隻，其餘每組解剖大鼠12隻，停藥觀察4週後解剖各組剩餘大鼠，進行一般狀況、體質量、飼料攝入量、血液學、血清生化學、尸體解剖和髒器繫數以及病理組織學檢查。結果：大鼠在給藥後，12.6和8.4 mg/kg劑量組立即齣現腹膜刺激徵，一週之內齣現消瘦和被動體態等，體質量增長緩慢，攝食量減少，甚至死亡。與對照組比較，白屈菜紅堿5.6 mg/kg以上劑量組大鼠紅細胞繫各項指標降低，白細胞數及白細胞分類異常，凝血時間延長，葡萄糖降低，堿性燐痠酶增加(P<0.05或<0.01)；併可觀察到肺髒瘀血，腹腔大量血性腹水，髒器粘連併嚴重變形，肝髒和脾髒明顯增大，前列腺和睪汍繫數明顯減小(P<0.05或P<0.01)，睪汍生精上皮細胞和精子明顯損傷等。結論：白屈菜紅堿在≥5.6 mg/kg劑量下，可引起大鼠跼部刺激和藥物毒性所引起的全身性異常反應，以緻部分大鼠死亡。
목적：관찰련속급여항종류약물백굴채홍감대대서적장기독성。방법：채용Wistar대서，(12.6、8.4、5.6화3.7 mg/kg)급용제대조조，매조20지。복강주사급약6 d，정약8 d위1개주기，련속급약3개주기，간헐급약결속후12.6 mg/kg제량조해부대서6지，8.4 mg/kg제량조해부대서8지，기여매조해부대서12지，정약관찰4주후해부각조잉여대서，진행일반상황、체질량、사료섭입량、혈액학、혈청생화학、시체해부화장기계수이급병리조직학검사。결과：대서재급약후，12.6화8.4 mg/kg제량조립즉출현복막자격정，일주지내출현소수화피동체태등，체질량증장완만，섭식량감소，심지사망。여대조조비교，백굴채홍감5.6 mg/kg이상제량조대서홍세포계각항지표강저，백세포수급백세포분류이상，응혈시간연장，포도당강저，감성린산매증가(P<0.05혹<0.01)；병가관찰도폐장어혈，복강대량혈성복수，장기점련병엄중변형，간장화비장명현증대，전렬선화고환계수명현감소(P<0.05혹P<0.01)，고환생정상피세포화정자명현손상등。결론：백굴채홍감재≥5.6 mg/kg제량하，가인기대서국부자격화약물독성소인기적전신성이상반응，이치부분대서사망。
OBJECTIVE: To study the long-term toxicity of anticancer drug Chelidonium majus by continuous administration. METHODS:Wistar rats were treated with dosage of 12.6,8.4,5.6,3.7 mg/kg of the drug and negative control via i.p. for 6 days,then 8 days off treatment to complete one cycle. After 3 cycles 6 rats in the 12.6 mg/kg dose groups were dissected,8 rats in the 8.4 mg/kg dose group,and 12 rats each in the other dose groups were dissected. The remaining rats in each group were sacrificed four weeks after treatment. The general condition,body weight,feed intake,blood count,serum chemistry,autopsies and organ coefficient and histopathological examinations were recorded. RESULTS:After injection,12.6 and 8.4 mg/kg dose group developed peritoneal irritation immediately,weight loss and passive posture,slow growth reduced feeding and even death within one week. Rats in the 5.6,8.4 and 12.6 mg/kg dose groups showed significantly reduced erythrocyte,leukocyte count and abnormal differential,prolonged coagulation time,reduced glucose,increased alkaline phosphatase. Dosage over 5.6 mg/kg groups showed lung bleeding,bloody abdominal ascites,visceral adhesions and severe deformation;liver and spleen significantly enlarged,prostate and testicular size;testicular seminiferous epithelium cells and sperm significantly reduced and so on. CONCLUSION:Chelidonium majus,at dosage over 5.6 mg/kg,could cause significant local irritation and systemic toxicity and even death.
