Study On The Pathological Mechanism Of Varicocele Vessel Remodeling

Objective: Through the study and comparison of different types and degrees of varicocele,the pathological changes of varicocele(VC)vessels were analyzed,and the pathogenesis and principle of VC were discussed.Methods: 1.Experimental group: A total of 25 patients,aged 19-35 years old,with a median age of 24 years old,who underwent sub-inguinal microsurgical varicocelectomy(MV)in the andrology Department of the Affiliated Hospital of Qingdao University from2018 to 2020 were selected.The intraoperative internal spermatic vein and external spermatic vein were taken as experimental samples.Control group: A total of 13 patients,aged 38-59 years old,median age 46 years old,who were diagnosed with testicular hydrocele and excluded VC in the andrology Department of Affiliated Hospital of Qingdao University at the same period,were selected,all patients underwent testicular hydrocele resection and turnover,and the normal spermatic vein obtained during the operation was used as control sample.The samples were divided into normal spermatic vein group,varicocele internal vein(> 3mm)group,varicocele internal vein(1-3mm)group,varicocele internal vein(< 1mm)group and varicocele external vein group.2.During the operation,the spermatic vein was enlarged 4-6 times with a microscope,and the intraoperative photos of the spermatic vein in each group were taken by screen capture function to compare the difference in the shape of the spermatic vein in each group.3.Hematoxylin-eosin staining(HE)and Transmission Electron microscopy(TEM)were used to observe the morphologic structure and ultrastructure of spermatic vein tissue in each group 4.Western Blot(WB)and Real-time quantitative Polymerase Chain Reaction(q PCR)were used to detect alpha-smooth muscle actin(α-SMA)and osteopontin(OPN)were significantly different in protein and m RNA levels in each vein.Results: 1.Appearance morphology: Compared with normal veins in the control group,dilated,tortuously,elongated varicose veins in the experimental group were seen intraoperatively,the color was dark red,and the varicose veins were severed and ligated to show hypertrophic vein wall.2.In terms of histological morphology and ultrastructure,there was no vein flap structure in the normal spermatic vein in the control group,but there were valvelike protrusion in the lumen.In the experimental group,the valvelike protrusion was not obvious.Compared with the normal veins in the control group,smooth muscle cells(SMC)hyperplasia and hyperplasia were observed under light microscopy in the varicose veins of the experimental group,with an arrangement of "medial longitudinal + central + external longitudinal".The fibrous tissue in the interstitial part also showed obvious hyperplasia,and local infiltration of neutrophils could be seen in the varicose veins wall.In the experimental group,chaos of SMC arrangement was observed under electron microscope,with increased intercellular collagen fiber aggregation,misarrangement,uneven thickness,irregular shape of SMC nucleus,folds,folds,multinucleation and other changes,necrosis and exfoliation of vascular endothelial cells and vacuolation of cytoplasmic mitochondria were observed in the internal spermatic vein(>3 mm).Occasionally trophoblastic capillaries could be seen in internal spermatic vein(>3 mm)and external spermatic vein wall.3.On the protein expression level: the expression of OPN in the external spermatic vein of the experimental group was different from that of the control group(P<0.05);the expression of α-SMA in the internal spermatic vein of the experimental group(>3 mm)was significantly different from that in the normal spermatic vein of the control group(P<0.01),the expression of α-SMA in the internal spermatic vein of the experimental group(1-3 mm)and the external spermatic vein was significantly different from that in the normal spermatic vein of the control group(P<0.05).4.On the m RNA level: the expression of OPN in the external spermatic vein of the experimental group was different from that of the control group(P<0.05).There was no difference in the expression ofα-SMA in the varicose veins of the experimental group compared with the normal veins of the control group(P> 0.05).Conclusion: 1.The occurrence and development of VC may be related to the vascular remodeling of the spermatic vein,mainly including abnormal hyperplasia of SMC,abnormal arrangement of collagen fibers,increase of dense bodies,and change of nuclear morphology,etc.,which provides an experimental basis for explaining the impaired vasomotor function of the spermatic vein and decreased antireflux ability in patients with VC.2.The expression of α-SMA and OPN in varicose veins was different from that in normal veins,suggesting the phenotypic changes in SMC,which provided pathological evidence for VC vascular remodeling.