| BackgroundLow intelligence is major clinical syndrome of dementia patient. Memory is basic intelligence factor, and easy to test, is an important criteria that tested improving status of intelligence.This project used existing vascular dementia model rat, integrated kidney asthenia with blood stasis syndrome of Chinese medicine, established kidney asthenia with blood stasis syndrome vascular dementia model rat which mixed weak and sthenis, and randomly divided them to several groups, given Kangxin Capsule decoction and its minor components decoctions. After treatment tested behavior change of the VD model rats. Under electron microscopy observed microstrucrures of nerve cells; and light microscopy observed expression of some related factors of immune-histology biochemistry; Neurotransmitters: Ach, Glu, 5-HT, DA, GABA of cerebral tissues were detected; peripheral blood Ach, CD3, CD4, CD8 and E2, T were tested. Observed Kangxin Capsule and its minor components are influenced in behaviors, memory, neurotransmitters, sex hormones, and immunity. Obtained basic theory and experimental trials that proved Chinese herbal medicine in treating kidney asthenia with blood stasis syndrome vascular dementia. Methods and Results Part IEstablished kidney asthenia with blood stasis syndrome vascular dementia model rat, and observed decoction of KANGXIN capsule and its minor components are influenced on behaviors, memory, neurotransmitter, sex hormone, and immunity of kidney asthenia with blood stasis syndrome vascular dementia. Methods: Used electric iron to burn and block both side vertebral arteries and amputated one side genital organ (testis or ovary) of rat, made kidney asthenia with blood stasis syndrome vascular dementia model rat. KANGXIN capsule complete components and its minor components, and Dihydroergotaxine group had been given for 1 month, at the same time established control model group (hadn't given any medication), each group were 10 rats. Complete components, kidney tonic, pancreas tonic, blood tonic with promoting blood circulation, and western medicine Dihydroergotaxine group. Used electron microscopy and light microscopy to observed nerve cells of hippocampus, hypothalamus, occipital lobe cortex of each group, and used flow cell cytometer to analysis peripheral blood CD3, CD4, CD8 of model rat. Results: 1. Behavior testing: swimming ability of kangxin capsule complete component group are higher than control, pancreas tonic groups (p<0.01), and western medicine group (p<0.05); Kangxin capsule complete component group's spatial probe test (times) is higher than the blood tonic with promoting blood circulation, and control group (p<0.05, P<0.01); 2. Under electron microscopy: reticulum, nuclear, mitochondrion, and rough endoplasmic of nerve cells of hippocampus, hypothalamus, occipital cerebral cortex of Kangxin capsule complete component are slighter swelling and reduce (other groups improved with difference scale), that are compared with control model group. Mitochondrion of hypothalamus of each group is appeared slightly swelling anddamage of microstructure is in difference scale, chromatin is concentrated. 3. Neurotransmitters: glutamic acid of hippocampus, hypothalamus are increase but no statistic significance, and glutamic acid level of occipital cerebral cortex of complete component are higher than pancreas tonic (p<0.01), Ach of the peripheral blood of kidney tonic group is higher than blood tonic with promoting blood circulation(p<0.05). 4. Expression of related factors of immune-histology biochemistry: ①Expression GFAP of hypothalamus of complete component group is lower thancontrol, kidney tonic group (P<0.05); expression of hippocampus of blood tonic with promoting blood circulation, complete component are lower than kidney tonic group (p<0.05); expression of hippocampus of western medicine is lower than control,kidney tonic group (p<0.05). ② Expression NF-κB of hypothalamus of blood tonicwith promoting blood circulation is lower than kidney tonic, pancreas tonic group (p<0.05); Expression of hippocampus of complete component is lower than westernmedicine group (p<0.01). ③ Expression C-fos of hippocampus of completecomponent, pancreas tonic group are higher than other group; Expression of hypothalamus of complete component is higher than the control, blood tonic with promoting blood circulation (p<0.01); Expression of hypothalamus of western medicine is higher than control group (p<0.01); expression of hippocampus of complete component is higher than control, kidney tonic, blood tonic with promoting blood circulation (p<0.01), and is higher than western medicine western (p<0.05); expression of hippocampus of pancreas tonic is higher than control, kidney tonic,western medicine (p<0.05). ④ Expression p75NGFR of hypothalamus of pancreastonic is lower than control (p<0.01); Expression of hypothalamus of blood tome with promoting blood circulation is lower than complete component, pancreas tonic group (p<0.01); expression of hypothalamus of kidney tonic is lower than control group (p<0.01); expression of hippocampus of complete component is lower than control group (p<0.01); expression of hippocampus of pancreas tonic is lower than blood tonic with promoting blood (p<0.05), and is lower than western medicine (p<0.01); expression of hippocampus of western medicine is higher than complete component, kidney tonic (p<0.01), and higher than blood tonic with promoting blood circulation(p<0.05). ⑤ Expression TrKA of hypothalamus of control group is lower thancomplete component, kidney tonic, pancreas tonic, western medicine group (p<0.01); Expression of hypothalamus of complete component is higher than pancreas tonic (p<0.01); expression of hypothalamus of blood tonic with promoting blood circulation is lower than complete component, kidney tonic, western medicine (p<0.01), and is lower than pancreas tonic (p<0.05); expression of hippocampus of blood tonic with promoting blood circulation is lower than the control group (p<0.05), and is lower than complete component, kidney tonic, western medicine (p<0.01).5. Flow Cell cytometer analysis: CD4/CD8 Ratio of complete component is higher than control, pancreas tonic, western medicine group (p<0.01), CD4/CD8 Ratio of blood tonic with promoting blood circulation is higher than control, pancreas tonic group (p<0.05).6. Sex hormone levels. E2/T Ratio of complete component and pancreas tonic is lower than blood tonic with promoting blood circulation and control group (p<0.01). E2 and E2/T ratio is higher than other male model rat group, E2 of male control group is higher than male complete component and kidney tonic group (p<0.05), E2/T ratio of male control group is higher than other group but not statistic significant.Part II Dependent on evidences and phenomenon of experimental animal trial, systematically observed and evaluated Kangxin capsule in treating kidney asthenia with blood stasis syndrome vascular dementia patients, who consulted and were treated in department of neurology of Xiamen TCM Hospital, period from June 2004 to March, 2005. All of them were diagnosed cerebral vascular accidence with cerebral injury by CT, MRI. Used diagnostic criteria for probable vascular dementia of the American Psychiatric Association. Diagnostic and Statistical of Manual of Mental Disorder, 4th ED (DSM-IV) 1994 revised; Diagnostic criteria for research studies-Report of the NINDS-AIREN International workshop. 1993; Chinese medicine diagnostic criteria of loss intelligence influenced social and occupation activities; and used "guideline of clinical research of new Chinese medicine in treating dementia" DOH of P.R.O.C, 1995, for the diagnosis of kidney asthenia with blood stasis with weak and sthenia syndrome; all of VD patients are qualified diagnostic criteria of Chinese and western medicine; Chinese medicine syndromes differentiation are qualified by Chinese medicine diagnostic criteria. Kidney asthenia with blood stasis syndrome VD patients are randomly divided into two groups: treating group (Kangxin capsule was given, 29 patients, 11 males, 17 females; average age is 61.03± 13.65, dosage: 0.3 g/capsule, 3 capsules/time, 3 times/day, for 1 month). Control group (Piracetam had been given, 22 patients, 12 males, 10 females, average age is 62.4286 ±11.61235, dosage: 0.4 g/tablet, 0.8 g/time, 3 times/day, and curative period same with treating group). Results:1. After treatment, Hachinski ischemic score of treating group is decrease compared with before (<7, p<0.01); after treatment, Hachinski ischemic score of control group is decrease compared with before (p<0.05); 2. After treatment score of MMSE is increase compared with before treatment, score of MMSE of treating group 29 patients is 23.3125≥20%, curative effect is obviously, score of MMSE of control 22 patients is 12.91<20%, NO significance. 3. After treatment, scores of Chinese ZHENGHOU is decrease compared with before (p<0.01). 4. After treatment, blood stasis syndrome is decrease compared with before (p<0.01).5. Flow Cell cytometer analysis: CD3, CD4, CD8 are increase, but CD3, CD4 no statistic significance. After treatment, CD8 is increase compared with before (p<0.05), NK % decrease to normal range (8%~16%).6. Male patient sex hormones tested: After treatment, E2/T. ratio is increase compared with before (p>0.05), E2 is increase compared with before (p<0.05); control group E2,T are increase compared with before treatment, but no statistic significance. Female patients' sex hormones tested: female E2, E2/T ratio of treatment group is increase compared with before (p<0.05), T is increase compared with before, but no statistic significant; E2, T, E2/T ratio of control group are increase compared with before, but no statistic significance.7. ET testing: After treatment ET level of treating and control group are decrease, which are compared before (p<0.05).8. Routing (blood, urine, feces) exams, blood chemistry exam before and after treatment of treating and control group are within normal range, no statistic significance.ConclusionPart I Kangxin capsule complete component and its minor component blood tonic with promoting blood circulation are able to increase CD4/CD8 ratio of kidney asthenia with blood stasis syndrome vascular dementia rats that means enhanced immunity. Under electron microscopy reticulum nuclear mitochondrion and rough endoplasmic of nerve cells of Hippocampus, hypothalamus, occipital cerebral cortex of complete components and blood tonic with promoting blood circulation are slighter swelling and reducer, nuclear is concentrated, compared with control model group. Hypothalamus of every group, there are different scale of swelling, vacuolated and damaged of microstructure and chromatin are concentrated, but hypothalamus of complete component and blood tonic with promoting blood circulation are slighter damage than other groups. Kangxin capsule complete component and blood tonic with promoting blood circulation group are able to prevent ischemic injury that induced actroglial cell activation, prevent neuron degeneration, slowed down apoptosis process of nerve cells, prevented apoptosis of nerve cell; increased glutamic acid of brain tissue, enhanced immunity of kidney asthenia with blood stasis syndrome of vascular dementia model rat, adjust the sex hormone level, made E2/T ratio from pathology basis become physiology balance. Complete component is able to obviously increase model rats swimming ability, spatial probe test (times), and decrease escape latency timesPart II Kangxin Capsule are obviously improved Hachinski ischemic score, and effectively improved cognitive ability, and depression syndrome of geriatric; improved kidney asthenia and blood stasis syndrome. Increase E2, T of male and female, improved physiology kidney asthenia of elders (E2, T were low). Decreased ET of kidney asthenia with blood stasis syndrome vascular dementia patients prevented aging process of nerve cells, protected ischemic injury of nerve cell. Before and after treatment, Routing (blood, urine, feces) exam, and blood chemistry are always within normal range, none abnormal, that proved Kangxin Capsule is safety and without harmful to VD patients, no side effect.
|
PDF Full Text Request