The Study Of Microflow Effects On Hepatic Sinusoid Blood Flow And Red Blood Cell Deformation And Functions

The liver plays an important role in many physiological functions which are closely related to the blood flow.The occurrence of many diseases in the liver is always accompanied by hemodynamic changes.Different from other capillaries,hepatic sinusoids,as the basic unit of hepatic blood flow,have their own special physiological microstructures and microenvironments.In hepatic sinusoids,there is a space between endothelial cells and hepatocytes,called the Disse space.Many sieve holes on the endothelial cells allow blood flows through directly into the Disse space for material exchange and signal transmission with the hepatocytes.When the liver is diseased,the size and distribution of the sieve holes on the endothelial cells also change,which complicates the blood flow in hepatic sinusoids.In addition,the Disse space is generally about 1 μm.When the flow characteristic size is reduced to micro scale,some phenomena neglected in macro flow become important.Therefore,the microflow effect on hepatic sinusoid blood flow cannot be ignored.The study of blood flow and microflow effects in the liver is of great scientific significance to the study of liver pathological mechanisms and physiological functions.In this thesis,the characteristics and mechanisms of microflow effects on blood flow,cell movement,deformation and function in hepatic sinusoids were studied.The main contents include:1.A lattice Boltzmann method suitable for hepatic sinusoid blood microflow was proposed.The immersed boundary method coupled with lattice Boltzmann numerical method was used.And three external force terms were introduced to simulate the effect of endodermal permeability,roughness of hepatic microvillus and collagen layer,and erythrocyte deformation on blood flow respectively.Based on the proposed calculation method,the dual-channel micorflow model of in vitro liver chip was firstly built.The numerical calculation results were compared with experimental results in vitro liver chip to verify the accuracy and effectiveness of calculation model and calculation method.Meanwhile,the flow velocity migration was found in the calculation results,which is consistent with the experimental results.2.The single channel blood flow model of hepatic sinsoid was built.The wall roughnesss effect of hepatocytes and microscale effects of Disse space were studied expecially.The results showed that the flow velocity in the Disse space was very small,and the distribution of the flow velocity in the hepatic sinusoid was determined by the endodethial layer permeability.The shear stress of blood flow on the surface of hepatocytes and endothelial cells showed a bidirectional phenomenon influenced by the permeability of the endodethelial cells and the thickness of the hepatic microvillus and collagen layer,and this phenomenon was related to the small size of the Disse space.The reliability of bidirectional results was verified by comparing the theoretical results with numerical results through theoretical derivation.The influence of blood microflow on the red blood cell deformation was also studied.The results showed that the endothelial cell permeability significantly affects the deformation index of red blood cells.3.The dual-branched blood flow model and the mass transport model of hepatic sinusoid was built to study the dual-branched effects on hepatic blood flow and the microflow effects on the mass transport.The formation of bypass pipes often occurs in hepatic sinusoids under the pathological conditions of liver fibrosis and cirrhosis.Therefore,the dual-branched blood flow model of hepatic sinusoid was further established to discuss the microflow of hepatic sinusoid blood in a more complex environment.According to the calculated results,the flow velocity of the dual-branched hepatic sinusoid showed a non-monotonic change with the permeability of the endodethlial cell due to the existence of the Disse space and branches.The influence of hepatic blood microflow on hepatic lipid metabolism was studied preliminarily with the mass transport model.The material transport process of hepatocytes converting free fatty acids into triglycerides and transporting them into hepatic sinusoids as lipoproteins was simulated.And the effect of endothelial layer permeability on lipid deposition in hepatic sinusoids was discussed.In this thesis,the lattice Blotzmann method suitable for hepatic sinusoid blood microflow was proposed.The dual-channel micorflow model of in vitro liver chip,the single channel blood flow model of hepatic sinsoid,the dual-branched model of hepatic sinusoidal flow and the mass transport model of hepatic sinusoid were built to study the micorflow effects on blood flow,cell movement,deformation and function in hepatic sinusoids.The bidirectional shear stress and non-monotonic flow velocity of blood flow in hepatic sinusoid were obtained.Through numerical simulation and comparison of experimental results,the influence of microflow effects on blood flow,such as roughness of hepatic microvillus,collagen deposition and microsize of Disse space in hepatic sinusoids,was illustrated.The results of this study provide a basis for understanding the relationship between blood flow characteristics and physiological function of hepatic sinusoids and the relationship between blood flow changes of hepatic sinusoids and pathogenesis under pathological conditions.