Zhang Jinshan,Li Long.Relationship between portal vein patency and changes of portal hemodynamics and portal venous pathology[J].Journal of Clinical Pediatric Surgery,2022,21(10):980-986.[doi:10.3760/cma.j.cn101785-202105061-014]
门静脉通畅状态对门静脉血流动力学和门静脉血管病理改变的影响研究
- Title:
- Relationship between portal vein patency and changes of portal hemodynamics and portal venous pathology
- Keywords:
- Portal Vein; Physiopathology; Portal Vein; Injuries; Portal Vein; Hemodynamics; Portal Pressure; Animal Experimentation
- 摘要:
- 目的 探讨门静脉通畅情况对门静脉血流动力学和门静脉血管病理生理的影响。方法 选取18只4~5 kg雄性成年新西兰白兔作为研究对象,采用随机数字表法将其分为3组:一组采用开腹后游离门静脉主干的方法,为对照(normal control,NC)组;一组采用套管将门静脉主干部分缩窄的方法,为肝外门静脉梗阻(extra-hepatic portal venous obstruction,EHPVO)组;一组采用在EHPVO模型制备14 d后将套管去除的方法,为可恢复性肝外门静脉梗阻(reversible extra-hepatic portal venous obstruction,r-EHPVO)组。所有模型于制作第14天和第28天时,测量门静脉压力、门静脉血流速度和门静脉血管直径。计算门静脉血管剪切力τ=4Q×η/π×r3[其中η为血黏度(Pa·s)、Q为血液流速(mL/s)、r为血管内半径(cm)]和门静脉血管周向应力T=ΔP×r/h[其中r为血管平均半径(cm),ΔP为管壁内外压强差(kPa),h为壁厚(cm)]。模型制作第28天时取门静脉主干血管制作病理切片,显微镜拍照,采用Image J测量内膜和中膜厚度、内膜和中膜面积。比较三组血管剪切力、周向应力、内膜和中膜厚度、内膜/中膜面积(I/M)和内膜/内膜中膜面积之和[I/(I+M)]的差异。分析剪切力与内膜厚度、周向应力与中膜厚度的相关性。结果 模型制作第28天时,与NC组相比,EHPVO组和r-EHPVO组的剪切力显著降低[EHPVO组比NC组为(0.392±0.041) Pa 比(0.772±0.039) Pa,P<0.001;r-EHPVO组比NC组为(0.690±0.042) Pa 比(0.772±0.039) Pa,P=0.009]、周向应力显著升高[EHPVO组比NC组为(34.002±3.128) kPa 比(15.706±0.867) kPa,P<0.001;r-EHPVO组比NC组为(22.329±3.350) kPa 比(15.706±0.867) kPa,P=0.002];但与EHPVO组相比,r-EHPVO组的剪切力明显升高[(0.690±0.042) Pa 比(0.392±0.041) Pa,P<0.001]、周向应力明显降低[(22.329±3.350) kPa 比(34.002±3.128) kPa,P<0.001]。与模型制作第14天去除套管前相比,模型制作第28天时r-EHPVO组的剪切力显著升高[(0.690±0.042) Pa 比(0.430±0.072) Pa,t=-8.079,P<0.001]、周向应力显著降低[(22.329±3.350) kPa 比(37.640±2.774) kPa,t=7.373,P=0.001],但均与模型制作第14天时去除套管后差异无统计学意义[剪切力:(0.690±0.042) Pa 比(0.650±0.058) Pa,t=-1.112,P=0.317;周向应力:(22.329±3.350) kPa 比(26.988±2.139) kPa,t=2.532,P=0.052]。EHPVO组的内膜厚度、I/M和I/(I+M)显著高于NC组和r-EHPVO组[EHPVO组内膜厚度比NC组内膜厚度为(11.35±1.47) μm 比(6.19±1.34)μm,P<0.001;EHPVO组内膜厚度比r-EHPVO组内膜厚度为(11.35±1.47) μm 比(7.88±1.72)μm,P=0.001;EHPVO组I/M比NC组I/M为(0.156±0.019)比(0.100±0.020),P<0.001;EHPVO组I/M比r-EHPVO组I/M为(0.156±0.019)比(0.117±0.011),P=0.002;EHPVO组I/(I+M)比NC组I/(I+M)为(0.135±0.014)比(0.091±0.016),P<0.001;EHPVO组I/(I+M)比r-EHPVO组I/(I+M)为(0.135±0.014)比(0.105±0.009),P=0.002],但NC组与r-EHPVO组的内膜厚度、I/M、I/(I+M)差异均无统计学意义[内膜厚度:(6.19±1.34)μm 比(7.88±1.72)μm,P=0.071;I/M:(0.100±0.020)比(0.117±0.011),P=0.104;I/(I+M):(0.091±0.016)比(0.105±0.009),P=0.089]。3组之间中膜厚度差异无统计学意义[(74.15±5.31) μm 比(62.97±5.65)μm 比(68.46±13.79)μm,P>0.05]。剪切力与内膜厚度呈负相关(r=-0.799,P<0.001)。周向应力与中膜厚度呈正相关(r=0.792,P<0.001)。结论 肝外门静脉梗阻与门静脉血流动力学及血管内膜变化密切相关,门静脉梗阻导致门静脉血流剪切力减少、周向应力增大及血管内膜增厚,重建门静脉入肝血流可逆转该状态。
- Abstract:
- Objective To explore the impact of portal vein patency on the changes of portal hemodynamics and portal venous pathology.Methods Eighteen New Zealand white rabbits were randomly divided into three groups of normal control (NC),extra-hepatic portal venous obstruction (EHPVO) and r-EHPVO (reversible extra-hepatic portal venous obstruction).They were created respectively by dissecting main portal vein after laparotomy,narrowing main portal vein with a cannula and removing the cannula at Day 14 after EHPVO modeling.Portal vein pressure,blood flow velocity and diameter of portal vein were measured at Day 14/28.Shear stress of portal vein was calculated by shear stress τ=4Q×η/π×r3 (η is fluid viscosity,Q fluid flow rate & r radius).Circumferential stress of portal vein was calculated by circumferential stress T=ΔP×r/h (r radius of portal vein,ΔP transmural pressure gradient & h wall thickness of portal vein).At Day 28,main portal vein was collected for pathological examination and thickness/area of intima and media were measured by Image J software.Shear stress,circumferential stress,intima and media thickness,intima area/media area (I/M) and intima area/sum of intima and media area [I/(I+M)] were compared among three groups.The correlations between shear stress and intima thickness and circumferential stress and media thickness were analyzed.Results At Day 28,as compared with NC group,shear stress dropped significantly [EHPVO vs.NC:(0.392±0.041) Pa vs.(0.772±0.039) Pa,P<0.001;r-EHPVO vs.NC:(0.690±0.042) Pa vs.(0.772±0.039) Pa,P=0.009]and circumferential stress increased markedly [EHPVO vs.NC:(34.002±3.128) kPa vs.(15.706±0.867) kPa,P<0.001;r-EHPVO vs.NC:(22.329±3.350) kPa vs.(15.706±0.867) kPa,P=0.002]in EHPVO and r-EHPVO groups;as compared with EHPVO group,shear stress spiked significantly [(0.690±0.042) Pa vs.(0.392±0.041) Pa,P<0.001]and circumferential stress declined markedly in r-EHPVO group[(22.329±3.350) kPa vs.(34.002±3.128) kPa,P<0.001].As compared with r-EHPVO group at Day 14 before removing cannula,shear stress significantly increased [(0.690±0.042) Pa vs.(0.430±0.072) Pa,t=-8.079,P<0.001]and circumferential stress dropped markedly in r-EHPVO group at Day 28 [(22.329±3.350) kPa vs.(37.640±2.774)kPa,t=7.373,P=0.001].However,shear and circumferential stresses showed no significant difference between r-EHPVO group at Day 28 and r-EHPVO group at Day 14 after removing cannula [shear stress:(0.690±0.042)Pa vs.(0.650±0.058)Pa,t=-1.112,P=0.317;Circumferential stress:(22.329±3.350) kPa vs.(26.988±2.139) kPa,t=2.532,P=0.052].Intimal thickness,I/M and I/(I+M) of EHPVO group were significantly higher than those of NC and r-EHPVO groups [intimal thickness:EHPVO vs.NC:(11.35±1.47) μm vs.(6.19±1.34) μm,P<0.001;EHPVO vs.r-EHPVO:(11.35±1.47) μm vs.(7.88±1.72) μm,P=0.001;I/M:EHPVO vs.NC:(0.156±0.019) vs.(0.100±0.020),P<0.001;EHPVO vs.r-EHPVO:(0.156±0.019) vs.(0.117±0.011),P=0.002;I/(I+M):EHPVO vs.NC:(0.135±0.014) vs.(0.091±0.016),P<0.001;EHPVO vs.r-EHPVO:(0.135±0.014) vs.(0.105±0.009),P=0.002].However,no difference existed in intimal thickness,I/M or I/(I+M) between NC and r-EHPVO groups [intimal thickness:(6.19±1.34) vs.(7.88±1.72) μm,P=0.071;I/M:(0.100±0.020) vs.(0.117±0.011),P=0.104;I/(I+M):(0.091±0.016) vs.(0.105±0.009),P=0.089].No significant difference existed in media thickness among three groups [(74.15±5.31) vs.(62.97±5.65) vs.(68.46±13.79) μm,P>0.05].A negative correlation existed between shear stress and intimal thickness(r=-0.799,P<0.001).And a positive correlation existed between circumferential stress and media thickness (r=0.792,P<0.001).Conclusion The patency of portal vein is significantly correlated with portal hemodynamics and intimal changes.Portal vein obstruction reduces shear stress and increases circumferential stress and intimal thickness.Restoring portal vein blood flow is beneficial to reverse these changes.
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备注/Memo
收稿日期:2021-5-31。
基金项目:国家自然科学基金(81770595、82170679);首都儿科研究所所级基金(GZ-2021-09)
通讯作者:张金山,Email:zjs851@163.com