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
2014年
4期
562-568
,共7页
裴天仙%王晶晶%滕晋莹%郭传敏%高广深%杨东%高绪聪%申秀萍%张宗鹏
裴天仙%王晶晶%滕晉瑩%郭傳敏%高廣深%楊東%高緒聰%申秀萍%張宗鵬
배천선%왕정정%등진형%곽전민%고엄심%양동%고서총%신수평%장종붕
酒石酸长春瑞滨%免疫系统%造血器官%毒性
酒石痠長春瑞濱%免疫繫統%造血器官%毒性
주석산장춘서빈%면역계통%조혈기관%독성
vinoreIbine tartrate%immune system%hemopoietic organ%toxicity
目的:从病理学角度研究酒石酸长春瑞滨( NVB)对大鼠免疫和造血系统的长期毒性作用。方法48只 SD 大鼠,雌雄各半,随机分为正常对照组和 NVB 5.0,10.0和20.0 mg·m-2组。NVB 静脉滴注给药,第1和第8天各给药1次,21 d 为1个周期,共给药4个周期。末次给药后14 d 腹主动脉取血,用ADVIA2120血液分析仪检测白细胞(WBC)、中性粒细胞(Neut)、淋巴细胞(Lym)和红细胞(RBC)数及网织红细胞千分比值(RET‰);剖取胸腺、胸骨骨髓、脾和肠系膜淋巴结进行组织病理学检查;精密称取胸腺和脾质量,计算脏器系数;取出股骨骨髓,进行骨髓涂片分类计数。结果与正常对照组比较,NVB 5.0,10.0和20.0 mg·m-2组雌雄大鼠外周血中 WBC,Neut,Lym 和 RBC 数及 RET‰均降低(P﹤0.05,P﹤0.01),其中雄性大鼠正常对照组 Neut 为(2.35±0.56)×109 L-1,NVB 各组分别降低为(1.66±0.44),(0.67±0.22)和(0.20±0.02)×109 L-1;雌性大鼠正常对照组 Neut 为(1.26±0.27)×109 L-1,NVB 各组分别降低为(1.14±0.56),(0.47±0.13)和(0.21±0.08)×109 L-1。骨髓涂片分类计数结果显示,粒系细胞比例降低( P ﹤0.05, P﹤0.01),其中雄性大鼠正常对照组粒系百分比为(42.7±6.1)%,NVB 各组分别降低为(28.8±5.3)%,(22.0±3.2)%和(18.9±3.9)%;雌性大鼠正常对照组粒系百分比为(35.4±3.0)%,NVB 各组分别降低为(31.2±4.7)%,(22.9±6.7)%和(20.8±4.2)%。胸腺系数降低(P﹤0.05,P﹤0.01),其中雄性大鼠正常对照组为0.36±0.04,NVB 各组分别降低为0.31±0.06,0.18±0.03和0.08±0.01;雌性大鼠正常对照组为0.29±0.06,NVB 各组分别降低为0.25±0.06,0.19±0.06和0.07±0.01。组织病理学检查结果显示,NVB 5.0,10.0和20.0 mg·m-2可致雌雄大鼠不同程度的胸腺萎缩和骨髓造血抑制,NVB 各剂量组亦可见不同程度的脾代偿性髓外造血细胞增多,肠系膜淋巴结均未见明显病理改变。结论 NVB 对 SD 大鼠免疫和造血系统具有毒性作用,表现为胸腺萎缩和骨髓造血抑制。
目的:從病理學角度研究酒石痠長春瑞濱( NVB)對大鼠免疫和造血繫統的長期毒性作用。方法48隻 SD 大鼠,雌雄各半,隨機分為正常對照組和 NVB 5.0,10.0和20.0 mg·m-2組。NVB 靜脈滴註給藥,第1和第8天各給藥1次,21 d 為1箇週期,共給藥4箇週期。末次給藥後14 d 腹主動脈取血,用ADVIA2120血液分析儀檢測白細胞(WBC)、中性粒細胞(Neut)、淋巴細胞(Lym)和紅細胞(RBC)數及網織紅細胞韆分比值(RET‰);剖取胸腺、胸骨骨髓、脾和腸繫膜淋巴結進行組織病理學檢查;精密稱取胸腺和脾質量,計算髒器繫數;取齣股骨骨髓,進行骨髓塗片分類計數。結果與正常對照組比較,NVB 5.0,10.0和20.0 mg·m-2組雌雄大鼠外週血中 WBC,Neut,Lym 和 RBC 數及 RET‰均降低(P﹤0.05,P﹤0.01),其中雄性大鼠正常對照組 Neut 為(2.35±0.56)×109 L-1,NVB 各組分彆降低為(1.66±0.44),(0.67±0.22)和(0.20±0.02)×109 L-1;雌性大鼠正常對照組 Neut 為(1.26±0.27)×109 L-1,NVB 各組分彆降低為(1.14±0.56),(0.47±0.13)和(0.21±0.08)×109 L-1。骨髓塗片分類計數結果顯示,粒繫細胞比例降低( P ﹤0.05, P﹤0.01),其中雄性大鼠正常對照組粒繫百分比為(42.7±6.1)%,NVB 各組分彆降低為(28.8±5.3)%,(22.0±3.2)%和(18.9±3.9)%;雌性大鼠正常對照組粒繫百分比為(35.4±3.0)%,NVB 各組分彆降低為(31.2±4.7)%,(22.9±6.7)%和(20.8±4.2)%。胸腺繫數降低(P﹤0.05,P﹤0.01),其中雄性大鼠正常對照組為0.36±0.04,NVB 各組分彆降低為0.31±0.06,0.18±0.03和0.08±0.01;雌性大鼠正常對照組為0.29±0.06,NVB 各組分彆降低為0.25±0.06,0.19±0.06和0.07±0.01。組織病理學檢查結果顯示,NVB 5.0,10.0和20.0 mg·m-2可緻雌雄大鼠不同程度的胸腺萎縮和骨髓造血抑製,NVB 各劑量組亦可見不同程度的脾代償性髓外造血細胞增多,腸繫膜淋巴結均未見明顯病理改變。結論 NVB 對 SD 大鼠免疫和造血繫統具有毒性作用,錶現為胸腺萎縮和骨髓造血抑製。
목적:종병이학각도연구주석산장춘서빈( NVB)대대서면역화조혈계통적장기독성작용。방법48지 SD 대서,자웅각반,수궤분위정상대조조화 NVB 5.0,10.0화20.0 mg·m-2조。NVB 정맥적주급약,제1화제8천각급약1차,21 d 위1개주기,공급약4개주기。말차급약후14 d 복주동맥취혈,용ADVIA2120혈액분석의검측백세포(WBC)、중성립세포(Neut)、림파세포(Lym)화홍세포(RBC)수급망직홍세포천분비치(RET‰);부취흉선、흉골골수、비화장계막림파결진행조직병이학검사;정밀칭취흉선화비질량,계산장기계수;취출고골골수,진행골수도편분류계수。결과여정상대조조비교,NVB 5.0,10.0화20.0 mg·m-2조자웅대서외주혈중 WBC,Neut,Lym 화 RBC 수급 RET‰균강저(P﹤0.05,P﹤0.01),기중웅성대서정상대조조 Neut 위(2.35±0.56)×109 L-1,NVB 각조분별강저위(1.66±0.44),(0.67±0.22)화(0.20±0.02)×109 L-1;자성대서정상대조조 Neut 위(1.26±0.27)×109 L-1,NVB 각조분별강저위(1.14±0.56),(0.47±0.13)화(0.21±0.08)×109 L-1。골수도편분류계수결과현시,립계세포비례강저( P ﹤0.05, P﹤0.01),기중웅성대서정상대조조립계백분비위(42.7±6.1)%,NVB 각조분별강저위(28.8±5.3)%,(22.0±3.2)%화(18.9±3.9)%;자성대서정상대조조립계백분비위(35.4±3.0)%,NVB 각조분별강저위(31.2±4.7)%,(22.9±6.7)%화(20.8±4.2)%。흉선계수강저(P﹤0.05,P﹤0.01),기중웅성대서정상대조조위0.36±0.04,NVB 각조분별강저위0.31±0.06,0.18±0.03화0.08±0.01;자성대서정상대조조위0.29±0.06,NVB 각조분별강저위0.25±0.06,0.19±0.06화0.07±0.01。조직병이학검사결과현시,NVB 5.0,10.0화20.0 mg·m-2가치자웅대서불동정도적흉선위축화골수조혈억제,NVB 각제량조역가견불동정도적비대상성수외조혈세포증다,장계막림파결균미견명현병리개변。결론 NVB 대 SD 대서면역화조혈계통구유독성작용,표현위흉선위축화골수조혈억제。
OBJECTlVE To study the Iong term toxicity of vinoreIbine tartrate(NVB)on rat immune and hematopoietic systems pathoIogicaIIy. METHODS SD Rats were randomIy divided into 4 groups:normaI controI group and NVB 5.0,10.0,and 20.0 mg·m-2 groups,each group containing 6 maIe and femaIe rats. The rats in NBV groups were administered different concentrations of NVB by intravenous drip on the 1st and 8th days,21 da cycIe,for 4 cycIes. On the 14th day after the Iast administration, white bIood ceIIs(WBC),neutrophiI(Neut),Iymphocytes(Lym),red bIood ceIIs(RBC)and reticuIo-cyte‰(RET‰)were detected by ADVIA2120 hematoIogy anaIyzer. Thymus,sternum marrow,spIeen and mesenteric Iymph nodes were observed by histopathoIogicaI examination. The thymus and spIeen were preciseIy weighed to obtain the reIative organ coefficients. Bone marrow smears were made for counting and cIassification. RESULTS Compared with normaI controI group,WBC,Neut,Lym,RBC and RET% of peripheraI bIood of NVB 5,10 and 20 mg·m-2 groups were decreased(P﹤0.05,P﹤0.01). The Neut vaIue of maIe rats was(2.35±0.56)×109·L-1 in normaI controI group,but was reduced to (1.66±0.44),(0.67±0.22)and(0.20±0.02)×109·L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The Neut vaIue of femaIe rats was(1.26± 0.27)× 109 L-1 in normaI controI group,but was reduced to(1.14±0.56),(0.47±0.13)and(0.21±0.08)×109 L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The resuIts of counting and cIassification of bone marrow smears showed that the myeIoid ceII ratio decreased(P﹤0.05,P﹤0.01). The myeIoid ceII ratio of maIe rats was(42.7±6.1)% in normaI controI group,but was reduced to(28.8±5.3)%,(22.0±3.2)% and(18.9±3.9)% in NVB 5,10 and 20 mg·m-2 groups. The myeIoid ceII ratio of femaIe rats in normaI controI group was(35.4±3.0)%, but was reduced to(31.2±4.7)%,(22.9±6.7)% and(20.8±4.2)% in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient was reduced(P﹤0.05,P﹤0.01). The thymus coefficient of maIe rats in normaI controI group was 0.36±0.04,but was reduced to 0.31±0.06,0.18±0.03 and 0.08±0.01 in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient of femaIe rats in normaI controI group was 0.29±0.06,but was reduced to 0.25±0.06,0.19±0.06 and 0.07±0.01 in NVB 5,10 and 20 mg·m-2 groups. Histopatho-IogicaI examination showed that thymus was atrophiedand bone marrow was suppressed. SpIeen com-pensatory extrameduIIary hematopoietic ceIIs were increased in NVB 5.0,10.0 and 20.0 mg·m-2 groups (maIe and femaIe)to different degrees,but the mesenteric Iymph nodes of NVB groups showed no sig-nificant pathoIogicaI changes. CONCLUSlON NVB has immune and hematopoietic toxicity on SD rats, as is showed by thymic atrophy and bone marrow suppression.