中华放射学杂志
中華放射學雜誌
중화방사학잡지
Chinese Journal of Radiology
2009年
2期
191-195
,共5页
李强%王茂强%段留新%宋鹏%敖国昆%廖洪波%宋晶莹
李彊%王茂彊%段留新%宋鵬%敖國昆%廖洪波%宋晶瑩
리강%왕무강%단류신%송붕%오국곤%료홍파%송정형
胰腺肿瘤%脂肪乳剂,静脉注射用%顺铂%放射摄影术,介入性%动物实验
胰腺腫瘤%脂肪乳劑,靜脈註射用%順鉑%放射攝影術,介入性%動物實驗
이선종류%지방유제,정맥주사용%순박%방사섭영술,개입성%동물실험
Pancreatic neoplasms%Fat emulsions,intravenous%Cisplatin%Radiography,interventional%Animal experimentation
目的:探讨经动脉灌注脂肪乳顺铂混合液,行胰腺局部灌注化疗治疗胰腺癌的效果及作用机制。方法24只健康杂种犬,按随机表法分为A、B、C、D组,每组6只。4组顺铂用量均为4 mg/kg。 A、B组以20%脂肪乳为溶剂,配制成顺铂-脂肪乳混合液,A组用量为2 ml/kg、B组用量为1 ml/kg;C、D组以生理盐水为溶剂,配制成顺铂-生理盐水溶液,C组用量为2 ml/kg、D组为1 ml/kg。置管至实验动物脾动脉开口部,根据各组的用药标准,分别将配制好的药物经动脉灌注到胰腺肿瘤区。分别于给药后即刻及3、5、10、20、30、40、50、60 min采集外周静脉血,60 min后取胰腺、胰周和肝、肾、脾等组织,测定血液和组织匀浆内顺铂的浓度,计算实验犬血液的时间-药物浓度曲线下面积( AUC)、初始药物浓度( C0)及生物半衰期( t1/2),并观察组织病理改变。组织染色采用HE染色。4组AUC、C0、t1/2间比较,采用方差分析,组间两两比较采用q检验;A、B组组织中顺铂浓度的比较用成组t检验,数据方差不齐时采用t′检验。结果 AUC、C0、t1/2在A组分别为(54.5±10.1)%、(2.6±0.5) mg/L、(16.7±3.6) min,B组分别为(18.3±6.0)%、(1.5±0.2) mg/L、(47.9±11.1) min, C组分别为(116.7±20.6)%、(6.5±0.4) mg/L、(10.5±2.8) min,D组分别为(126.6±30.7)%、(5.5±0.4) mg/L、(10.1±3.1) min,4组间比较差异有统计学意义( AUC、C0、t1/2的 F值分别为42.42、249.61、12.48,P值均<0.01)。 A、B组的AUC和C0明显低于C、D组( A组与C组、B组与D组比较AUC, t值分别为6.64、8.49,比较C0的t值分别为16.34、22.30,P值均<0.01),t1/2明显长于C、D组(A组与C组、B组与D组比较,t值分别为3.36、3.71,P值均<0.01));B组的AUC、C0明显低于A组(t值分别为7.57、5.48,P值均<0.01),t1/2长于A组(t值为3.22,P<0.05)。 B组的胰左叶、胰腺角中顺铂含量较A组增高[B组分别为0.18、0.18 mg/L,A组分别为0.05、0.05 mg/L],差异有统计学意义( t值分别为2.52、2.73,P值均<0.05);胰腺右叶和脾脏组织中的顺铂浓度两组比较差异无统计学意义[B组分别为0.11、0.29 mg/L,A组分别为0.07、0.24 mg/L,P值均>0.05]。病理检查所见:A、B组犬胰腺、胰周淋巴结、肝脏、脾脏有少量炎细胞浸润及血管扩张充血,血管内可见脂肪乳颗粒。其余组织及C、D组病理检查未见异常。结论脂肪乳作为溶剂可使顺铂在胰腺的浓度显著增高、进入血循环的药物总量减少。进入组织的药物量与脂肪乳内所含顺铂的浓度有关,浓度越高,进入组织内的药物越多。
目的:探討經動脈灌註脂肪乳順鉑混閤液,行胰腺跼部灌註化療治療胰腺癌的效果及作用機製。方法24隻健康雜種犬,按隨機錶法分為A、B、C、D組,每組6隻。4組順鉑用量均為4 mg/kg。 A、B組以20%脂肪乳為溶劑,配製成順鉑-脂肪乳混閤液,A組用量為2 ml/kg、B組用量為1 ml/kg;C、D組以生理鹽水為溶劑,配製成順鉑-生理鹽水溶液,C組用量為2 ml/kg、D組為1 ml/kg。置管至實驗動物脾動脈開口部,根據各組的用藥標準,分彆將配製好的藥物經動脈灌註到胰腺腫瘤區。分彆于給藥後即刻及3、5、10、20、30、40、50、60 min採集外週靜脈血,60 min後取胰腺、胰週和肝、腎、脾等組織,測定血液和組織勻漿內順鉑的濃度,計算實驗犬血液的時間-藥物濃度麯線下麵積( AUC)、初始藥物濃度( C0)及生物半衰期( t1/2),併觀察組織病理改變。組織染色採用HE染色。4組AUC、C0、t1/2間比較,採用方差分析,組間兩兩比較採用q檢驗;A、B組組織中順鉑濃度的比較用成組t檢驗,數據方差不齊時採用t′檢驗。結果 AUC、C0、t1/2在A組分彆為(54.5±10.1)%、(2.6±0.5) mg/L、(16.7±3.6) min,B組分彆為(18.3±6.0)%、(1.5±0.2) mg/L、(47.9±11.1) min, C組分彆為(116.7±20.6)%、(6.5±0.4) mg/L、(10.5±2.8) min,D組分彆為(126.6±30.7)%、(5.5±0.4) mg/L、(10.1±3.1) min,4組間比較差異有統計學意義( AUC、C0、t1/2的 F值分彆為42.42、249.61、12.48,P值均<0.01)。 A、B組的AUC和C0明顯低于C、D組( A組與C組、B組與D組比較AUC, t值分彆為6.64、8.49,比較C0的t值分彆為16.34、22.30,P值均<0.01),t1/2明顯長于C、D組(A組與C組、B組與D組比較,t值分彆為3.36、3.71,P值均<0.01));B組的AUC、C0明顯低于A組(t值分彆為7.57、5.48,P值均<0.01),t1/2長于A組(t值為3.22,P<0.05)。 B組的胰左葉、胰腺角中順鉑含量較A組增高[B組分彆為0.18、0.18 mg/L,A組分彆為0.05、0.05 mg/L],差異有統計學意義( t值分彆為2.52、2.73,P值均<0.05);胰腺右葉和脾髒組織中的順鉑濃度兩組比較差異無統計學意義[B組分彆為0.11、0.29 mg/L,A組分彆為0.07、0.24 mg/L,P值均>0.05]。病理檢查所見:A、B組犬胰腺、胰週淋巴結、肝髒、脾髒有少量炎細胞浸潤及血管擴張充血,血管內可見脂肪乳顆粒。其餘組織及C、D組病理檢查未見異常。結論脂肪乳作為溶劑可使順鉑在胰腺的濃度顯著增高、進入血循環的藥物總量減少。進入組織的藥物量與脂肪乳內所含順鉑的濃度有關,濃度越高,進入組織內的藥物越多。
목적:탐토경동맥관주지방유순박혼합액,행이선국부관주화료치료이선암적효과급작용궤제。방법24지건강잡충견,안수궤표법분위A、B、C、D조,매조6지。4조순박용량균위4 mg/kg。 A、B조이20%지방유위용제,배제성순박-지방유혼합액,A조용량위2 ml/kg、B조용량위1 ml/kg;C、D조이생리염수위용제,배제성순박-생리염수용액,C조용량위2 ml/kg、D조위1 ml/kg。치관지실험동물비동맥개구부,근거각조적용약표준,분별장배제호적약물경동맥관주도이선종류구。분별우급약후즉각급3、5、10、20、30、40、50、60 min채집외주정맥혈,60 min후취이선、이주화간、신、비등조직,측정혈액화조직균장내순박적농도,계산실험견혈액적시간-약물농도곡선하면적( AUC)、초시약물농도( C0)급생물반쇠기( t1/2),병관찰조직병리개변。조직염색채용HE염색。4조AUC、C0、t1/2간비교,채용방차분석,조간량량비교채용q검험;A、B조조직중순박농도적비교용성조t검험,수거방차불제시채용t′검험。결과 AUC、C0、t1/2재A조분별위(54.5±10.1)%、(2.6±0.5) mg/L、(16.7±3.6) min,B조분별위(18.3±6.0)%、(1.5±0.2) mg/L、(47.9±11.1) min, C조분별위(116.7±20.6)%、(6.5±0.4) mg/L、(10.5±2.8) min,D조분별위(126.6±30.7)%、(5.5±0.4) mg/L、(10.1±3.1) min,4조간비교차이유통계학의의( AUC、C0、t1/2적 F치분별위42.42、249.61、12.48,P치균<0.01)。 A、B조적AUC화C0명현저우C、D조( A조여C조、B조여D조비교AUC, t치분별위6.64、8.49,비교C0적t치분별위16.34、22.30,P치균<0.01),t1/2명현장우C、D조(A조여C조、B조여D조비교,t치분별위3.36、3.71,P치균<0.01));B조적AUC、C0명현저우A조(t치분별위7.57、5.48,P치균<0.01),t1/2장우A조(t치위3.22,P<0.05)。 B조적이좌협、이선각중순박함량교A조증고[B조분별위0.18、0.18 mg/L,A조분별위0.05、0.05 mg/L],차이유통계학의의( t치분별위2.52、2.73,P치균<0.05);이선우협화비장조직중적순박농도량조비교차이무통계학의의[B조분별위0.11、0.29 mg/L,A조분별위0.07、0.24 mg/L,P치균>0.05]。병리검사소견:A、B조견이선、이주림파결、간장、비장유소량염세포침윤급혈관확장충혈,혈관내가견지방유과립。기여조직급C、D조병리검사미견이상。결론지방유작위용제가사순박재이선적농도현저증고、진입혈순배적약물총량감소。진입조직적약물량여지방유내소함순박적농도유관,농도월고,진입조직내적약물월다。
Objective To approach the mechanism and efficacy of regional intra-arterial infusion chemotherapy with the mixture of lipid emulsion-CDDP ( LE-CDDP ) for treatment of locally advanced pancreatic cancer.Methods Twenty-four health dogs were divided into four groups ( group A,B,C, and D).The dosage of CDDP was used in 4 mg/kg/body weight for each animal.The 20%LE, as a solvent, was used in the experimental animals with 2 ml/kg/body weight ( group A ) and 1 ml/kg/body weight ( group B) , respectively.Normal sodium ( NS) as a solvent was used as control with 2 ml/kg/body weight (group C) and 1 ml/kg/body weight (group D), respectively.The LE-CDDP mixture and the NS-CDDP mixture were infused into the proximal segment of splenic artery under the DSA, with transfemoral arterial approach.Blood samples were collected after infusion at 0,3,5,10,20,30,40,50,60 min and the tissues were obtained after the 60 min′s blood sample was collected.Blood samples, absorbent gland in peripancreas, liver, spleen, kidney, heart, portal vein, the superior segment of jejunal and pancreas and parapancreatic tissues were obtained for CDDP concentration analysis and histopathologic examination. Results The values of the area under curve ( AUC ) , the incipient serum concentration ( C0 ) and the elimination half-life ( t1/2 ) of the serum CDDP concentration-time curve in four groups were A ( 54.5 ± 10.1)%,(2.6 ±0.5 ) mg/L, ( 16.7 ±3.6 ) min;B ( 18.3 ±6.0 )%, ( 1.5 ±0.2 ) mg/L, ( 47.9 ± 11.1) min;C (116.7 ±20.6)%, (6.5 ±0.4) mg/L, (10.5 ±2.8) min and D (126.6 ±30.7)%, (5.5 ±0.4) mg/L, (10.1 ±3.1) min, respectively.There were significant difference among these four groups (F(AUC) =42.42, F(C0) =249.61, F(t1/2) =12.48, P<0.01).The values of AUC and C0 in the group A were significantly lower than those in the group C (t(AUC) =6.64,t(C0) =16.34, P<0.01), and the corresponding values in the group B being also significantly lower than those in the group D (t(AUC) =8.49, t(C0) =22.30, P<0.01).The value t1/2 in the group A was significantly longer than that of in the group C (t=3.36, P<0.01), and that of group B was also significantly longer than that of group D (t=3.71, P<0.01).The values of AUC and C0 in the group B were significantly lower than those in the group A (t(AUC) =7.57, t(C0) =5.48, P<0.01), and the value t1/2 in the group B was significantly longer than that in the group A (t=3.22, P<0.05).The concentrations of the left lobe and horn of pancreas were higher in the group B (0.18, 0.18 mg/L) than those in the group A (0.05, 0.05 mg/L)(t=2.52, 2.73, P<0.05 ) .The tissue CDDP concentration of the right lobe of pancreas and spleen were no significant difference between group A ( 0.11, 0.29 mg/L ) and group B ( 0.07, 0.24 mg/L ) ( P >0.05 ) . Perivascular lymphocytic and neutrophilic infiltration, congestion and hemorrhage were found in the pancreas, parapancreatic absorbent gland, liver and spleen in the group A and group B.The micro-particles of intralipid were present in the capillary vessel of these tissues.No specific pathological changes were found in other groups and organs.Conclusions The regional intra-arterial infusion with LE-CDDP mixture could increase the pancreatic CDDP concentration, meanwhile, it also could decrease the serum CDDP concentration.The more of the CDDP concentration in the LE-CDDP mixture, the more CDDP concentration at the pancreatic tissue accordingly.