The Clinical Effect Of Gandouling Tablets On Hepatolenticular Degeneration With Cognitive Disorder And The Potential Effect Mechanism Through Copper Overload Rats Model

Objective: To observe the clinical effect of Gandouling tablets on hepatolenticular degeneration(HLD) with cognitive disorder; and to observe the effects Gandouling tablets on the behavior, hippocampal synaptic structure in rats and the expression of Nerve growth factor(NGF) through copper overload rats model, so as to further discover the potential effect mechanism.Methods:(1) Sixty HLD cognitive disorder patients meeting the given criteria were selected. Patients were divided by computer randomly into Chinese Medicine Treatment Group(30 patients) and Western Medicine Comparison Group(30 patients). While receiving the normal treatment, Chinese Medicine Treatment Group were given Gandouling tablets and Western Medicine Comparison Group oxiracetam. The task was to observe the clinical effect, and the changes of ADAS-Cog, ADL and traditional Chinese medicine(TCM) syndrome assessment of the above two groups.(2) Build copper overload rats model and test the learning and memorizing ability of the rats by means of Morris Water Maze; Observe the pathological changes of the Cornu Ammon 1 under electron microscope; and observe the expression of the Cornu Ammon 1 NGF through immunohistochemical method. Results:(1) Clinical effect: The general clinical effect of the two groups did not show much difference(P>0.05), indicating the similar effect of the Chinese Medicine Treatment Group and Western Medicine Comparison Group;(2) Cognizance and abilities of organizing daily life: the ADAS-Cog assessment of the two groups both scored less after treatment and the difference of the data before and after treatment was statistically significant(P﹤0.01). However, the data difference of the two groups after treatment was not statistically significant(P>0.05), indicating the similar effect of Gandouling tablets and oxiracetam on improving HLD patients’ cognitive disorder. The ADL assessment of the two groups both scored less after treatment and the difference of the data before and after treatment was statistically significant(P﹤0.01); but it was of no statistical significance of the data difference after treatment of the two groups(P>0.05), indicating the similar effect of Gandouling tablets and oxiracetam on improving HLD patients’ abilities of organizing daily life.(3) TCM syndrome: The SDSVD scores of both groups decreased at a certain scale(P<0.01), but the Treatment Group had a bigger SDSVD drop after treatment, and the difference of the two groups after treatment was statistically significant(P<0.05), indicating that Gandouling tablets and oxiracetam can both improve the TCL syndrome whilst Gandouling tablets excels oxiracetam.(4) Index of Rats Behavior: With training going on, the time spent by all groups of rats on escaping incubation became less gradually. Compared with the Blank Group, rats of the Model Group showed obvious degeneration of learning and memorizing abilities. Despite that all the groups spent less and less time on escaping incubation as training went on, the Gandouling tablets and oxiracetam Groups clearly showed better signs than the Model Group(P<0.01). The frequency of the Model Group rats crossing the platform and its quadrants was evidently less than that of the Blank Group(P<0.01). The frequency of the Gandouling tablets and Oxiracetam Groups rats crossing the platform and its quadrants was clearly more than that of the Model Group(P<0.01), but still less than that of the Blank Group. In terms of the percentage of the swimming distance in the targeted quadrant, the Model Group was much less than the Blank Group(P<0.01), while the Gandouling tablets and Oxiracetam Groups were much higher than the Model Group(P<0.01), almost reached the level of the Blank Group(P>0.05). The difference was not statistically significant(P>0.05).(5) Synaptic ultrastructure of rats’ Cornu Ammon 1: By observing the synaptic ultrastructure of the Cornu Ammon 1 under electron microscope and statistical analysis, no big difference was noted in terms of the synaptic gap(P>0.05). Compared with the Model Group, there was an obvious increase in the interface curvature rate and active zone length of the Gandouling tablets Group. But the difference compared with the Oxiracetam Group had no statistical significance(P>0.05). Compared with the Blank Group, the interface curvature rate of the Gandouling tablets Group increased slightly(P<0.05), and it was of no statistical significance regarding increasing the active zone length(P>0.05).(6) Expression of the Cornu Ammon 1 NGF: Compared with the Blank Group, the expression of the Cornu Ammon 1 NGF of the Modeling Group was clearly weaker observed under the light microscope(P<0.01). The expression of the Gandouling tablets and Oxiracetam Groups were clearly stronger than that of the Model Group, and the difference was statistically significant(P<0.01); Compared with the Oxiracetam Group, the NGF expression of the Gandouling tablets Group had no obvious difference(P>0.05). Conclusions:(1) Gandouling tablets and oxiracetam l are both able to delay the further impairment of the HLD patients with cognitive disorder and improve the negative symptoms and patients’ abilities of organizing daily life for a higher quality of living; but Gandouling tablets has a better effect in improving patients’ TCM syndrom than oxiracetam and there is no sign of significant side effects;(2) Rats under copper overload model appear to have learning and memorizing disorders. The model will damage the synaptic ultrastructure of the Cornu Ammon 1 and weaken the expression of the Cornu Ammon 1 NGF;(3) There is a possible connection between the mechanism of Gandouling tablets treating HLD cognitive disorder and its function of strengthening the synaptic structure of the Cornu Ammon 1 and improving the NGF expression.