| Objective Whether patients with WD have change of the cerebral blood flow and vascular damage; To observe the effect of Gan Dou Ling on cerebral vascular injure in patients with Wilson disease. Gan Dou Ling of TX pathological morphological changes of cerebral tissues in mice.Methods Clinical part:Comparison of 60 WD patients and healthy group.We observe two groups change of ultrasonic detection(ultrasonic cerebrovascular function detector)and transcranial doppler(TCD)colour to exceed, magnetic resonance perfusion imaging,blood vessel damage factor(von willebrand factor(v WF), thrombosis, regulatory proteins(TM)and endothelial cell protein C receptor(EPCR), homocysteine(HCY)).60 patients with WD were randomly divided into treatment group and control group.The treatment group with Gan Dou Ling and DMPS medicine therapy.The control group only treated with DMPS. The changes of the above indexes were observed before and after treatment in 2 groups Experiment part: TX mice were randomly divided into model group, Gan Dou Ling group, penicillamine group. DL mice as control group.After different treatment, the 4groups are detected the blood vessel damage factor changes and cerebrovascular pathological changes, ultrastructural changes.Ultrastructural changes were observed under electron microscope. The expression of ICAM-1 and VCAM-1 in cerebral vessels was observed by immunohistochemistry.Results Clinical parts:(1)Ultrasonic cerebrovascular function testing results: WD group of patients with bilateral carotid artery peak velocity, average velocity and averagevelocity of minimum flow is lower than healthy group(P > 0.05); The bilateral common carotid artery dynamic resistance, bilateral peripheral resistance, pulse wave velocity and characteristic impedance of WD group were higher than that of healthy group(P > 0.05). After treatment, the maximum flow rate, the minimum flow rate, the mean velocity of blood flow, and the mean blood flow rate were increased in the treatment group compared with those before treatment(P > 0.05);After treatment,there was no significant change in peripheral resistance, dynamic resistance, pulse wave velocity and characteristic impedance before and after treatment in the treatment group(P > 0.05).There were no significant changes in the indexes of bilateral common carotid arteries in the control group(P > 0.05).(2) TCD results:The peak systolic velocity of LACA and LMCA in WD group was lower than the healthy group(P<0.05). The peak systolic velocity of RMCA and RACA was lower than the healthy group(P<0.01);The end diastolic blood flow velocity of RPCA was lower than that of healthy group(P<0.05);The end diastolic blood flow of LMCA, LACA, LPCA, RMCA, RACA was lower than the healthy group(P<0.01);The mean velocity of LMCA, LACA, RMCA,RACA were lower than the healthy group(P<0.01).The mean velocity of LPCA, RPCA were lower than that of healthy group(P<0.05);There was no significant difference in the PI value between the WD group and the healthy group(P>0.05).After treatment, the systolic peak velocity of LACA, LMCA, RMCA, RACA of the treatment group were increased compared with before treatment(P<0.01),The peak systolic velocity of RPCA and LPCA were higher than before treatment(P<0.05);The end diastolic velocity of LMCA,LACA, RMCA and RACA were higher than that before treatment(P <0.01);The end diastolic velocity of RPCA and LPCA were higher than that before treatment(P<0.05);The mean blood flow velocity of LMCA, LACA, RMCA, RACA, LPCA and RPCA was higher than that before treatment(P <0.01);There was no significant statistical significance in the treatment of PI value of each blood vessel before treatment(P>0.05).In the control group, there was no statistical significance in the peak systolicvelocity, end diastolic velocity, mean blood flow velocity and PI value before treatment(P>0.05).After treatment, the systolic peak velocity and mean blood flow velocity of LACA and RMCA in the treatment group were compared with that of the control group after treatment(P <0.05);After treatment, the peak systolic velocity and average velocity of RACA in the treatment group were compared with that of the control group after treatment(P <0.01).(3) Magnetic resonance perfusion imaging results:Compared with the healthy group,there was no statistical significance of bilateral thalamus r CBF in the WD group(P>0.05),The bilateral caudate nucleus area, bilateral caudate nucleus head area r CBF numerical reduction(P<0.01).After treatment, the bilateral caudate nucleus area and the area of bilateral nuclear r CBF in the treatment group were higher than those before treatment.(P<0.05);There was no significant change in the control group(P >0.05).After treatment, the r CBF value in the right side of the treatment group was significantly higher than that in the control group after treatment(P<0.01);Compared with the control group, the value of r CBF in the area of the left side of lenticular nucleus was increased(P<0.05).(4) The results of vascular injury factor:Compared with the healthy group, the HCY,v WF, TM and EPCR values of WD group were increased(P<0.01).After treatment,there was a significant difference in the decrease of Hcy in the treatment group(P<0.05),VWF, TM, EPCR values were significantly decreased, there is a significant difference(P <0.01); After treatment, EPCR, v WF values of the treatment group were lower than in the control group(P<0.01);TM value was lower than that of control group(P<0.05).Part of the experiment:(1)Determination of vascular injury factor:Compared with the control group, Hcy, v WF, TM, EPCR value of the model group were significantly increased(P<0.01)?Compared with the model group, the Hcy, v WF and EPCR values of the Gan Dou Ling group were decreased(P<0.05),TM values decreased significantly(P<0.01).Compared with model group, there was no statisticalsignificance of EPCR, v WF, TM and Hcy value in the Penicillin group(P>0.05).Compared with the group, the value of Hcy, v WF, TM, and EPCR in the Gan Dou Ling group decreased(P<0.05).(2) Cerebral vascular pathological changes:H-E staining:The cerebral blood vessel endothelial cells of the model group, the Gan Dou Ling group and the Penicillin group had different degrees of edema and degeneration.Neuronal cells have varying degrees of degeneration and necrosis.In the model group, the damage of the model group was lower than that of the model group.The damage of Gan Dou Ling group and Penicillin group were less than that of the model group.Transmission electron microscope observation:Different degrees of degeneration and necrosis of the cerebral vascular endothelial cells and neurons in the brain.Mitochondria vacuoles, fuzzy and even disappear. Model group was the most serious damage. Damage of the Gan Dou Ling was the lightest.(3)Immunohistochemical results:Changes of blood vessels in ICAM-1immunostaining:Compared with the blank group, the expression of ICAM-1 increased in model group(P<0.01);Compared with the model group, the expression of ICAM-1 was lower in the Gan Dou Ling group(P<0.01);Compared with the model group, the low expression of ICAM-1 in the Penicillin group( P<0.05);Compared with the Penicillin group,the low expression of ICAM-1 in the Gan Dou Ling group(P<0.05);Changes of blood vessels in VCAM-1 immunostaining:Compared with the blank group, the expression of ICAM-1 increased in model group(P<0.01);Compared with the model group, the expression of ICAM-1 was lower in the Gan Dou Ling group(P<0.01);Compared with the model group, the low expression of ICAM-1 in the Penicillin group( P<0.01);Compared with the Penicillin group,the low expression of ICAM-1 in the Gan Dou Ling group(P<0.05);Conclusion(1)WD patients with vascular injury.Injury showed a decrease of blood flow velocity inthe middle and small artery.The local cerebral blood flow in the area of the nuclear area and caudate nucleus was decreased,and Increased expression of vascular injury factor.But the hemodynamic changes of common carotid artery were not obvious.(2)Gan Dou Ling can improve the blood flow of small and medium sized blood vessels and Increase the cerebral blood flow in the area of the nuclear area and caudate nucleus in WD patients.Reducing vascular damage factor.(3)The TX mouse vascular damaged and the pathological morphological changes.Increased vascular injury factor levels.(4)Gan Dou Ling can improve TX mice vascular injury and have a protection effect on blood vessels.It can reduce the pathological injury of endothelial cells and neurons, and reduce the vascular damage factor. |
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