Study On The Central Control Mechanism Of Hypertensive

Object:In order to verify the stable TCM syndrome window(SHR 14-18 weeks of age) and establish the "disease and syndrome combined" animal model, we have done three kinds of tests:macro characterization and behavioral tests, micro physicochemical indexes and prescription disproof. Further, in order to explore the central control area of the SHR rats with liver fire hyperactivity syndrome, the test of brain resting state BOLD was done. We used ASL to test the cereal blood flow of the related brain areas and checked the neurotransmitter concentration of the central area by the method of High-performance liquid chromatography(HPLC), to explore the mechanism of central regulation effect of the SHR with hyperactivity syndrome.Methods:1 According to the judgment methods of hypertension with liver fire hyperactivity syndrome established in our previous research, SHR were screened for liver fire hyperactivity, and divided into model group, Sancao Jiangya Decoction group, Sini Decoction group and Nifedipine group; SHR with no liver fire hyperactivity syndrome were called non-model group; Wistar-Kyoto rats (WKY) were normal group. The macro characterization, open field test, revolving tolerance test, irritation degree score and blood pressure were dynamically collected or carried out from 12-20 weeks of age. And treated drug group rats in the syndromes of time window (14-18 weeks of age) with Sancao Jiangya Decoction, Sini Decoction and Nifedipine. ELISA method was carried out to check the serum content of angiotensinll (ANGII),5-hydroxytryptamine (5-HT), norepinephrine (NE), endothelin1 (ET1) respectively after 4 weeks and 6 weeks drug treatment.2 Using Bruker PhamaScan 7T of Bruker company of Germany to examine rat brain. The tested group were the model group, drug administration group (Sancao Jiangya Decoction) and the nomoal group. And they were screened when they were 14,16,18 weeks of age. The experimental rats accepted the test of T2-weighed image, resting state BOLD, and Arterial Spin Labeling (ASL) in sequence. In order to explore the regulative region of central nerous system, amplitude of lowfrequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity with SPM8 software.With the Bruker PhamaScan 7T’s own software, the information of the cerebral blood flow (CBF) of the whole brain blood flow and Region of Interest (ROI) (left and right hypothalamus, left and right hippocampus, and left and right cortex) was collected.3 High-performance liquid chromatography (HPLC) method was used to detecte the neurotransmitter (NE), epinephrine (E), dopamine (DA),3,4-Dihydroxyphenylacetic acid; Homoprotocatechuic acid (DOPCA),5-hydroxytryptamine (5-HT),5-hydroxy indole acetic acid (5-HIAA) of hypothalamus of rats in model group, drug administration group (Sancao Jiangya Decoction) and normal group when they were 14,18 weeks of age.Results:1 Dynamical acquisition of the macro characterization, behavior evaluation and the blood pressure showed:the hypertensive rats in the model group showed liver fire hyperactivity syndrom in 14-18 weeks old steadily; The macro characterization of drug group improves remarkably with the treatment of Sancao Jiangya Decoction, and the total distance and Frequency occurence of open field test results was lower than model group; irritable degree score and revolving tolerance time have improved in different degree, liver fire hyperactivity symptoms of the no model group rats gradually aggravate with increasing age; blood pressure in model group increased gradually, higher than the drug group. The trend was obvious and the beginning of the blood pressure decreased from 16 weeks of age, the age of 18 weeks the blood pressure was significantly lower than that of model group, blood pressure of no liver fire hyperactivity group was gradually increased but there was no significant difference with the model group.2 Resting state BOLD image analysis of hypertensive rats with liver fire hyperactivity syndrome in the brain region was concentrated in the limbic system, including the hippocampus, hypothalamus preoptic area and hypothalamus optic zone, nodules, hypothalamus, pontine tegmentum of midbrain periaqueductal gray and other regions which were related to emotion and behavior.3 ASL method for the detection of cerebral blood flow showed that compared with the control group, the 14-18 week old model group, model group, and drug group showed higher perfusion and hybrid hypoperfusion. CBF of rats in each group showed a decreasing trend with the increasing age. The model group compared with the model group CBF were lower, at the age of 18 weeks of model group were lower than that of blood in model group, with statistical significance in cerebral cortex, left hippocampus, right of regional differences (P<0.05). Sancao Jiangya Decoction drug intervention CBF value is still continued to decline, Sancao Jiangya Decoction may not play a role through improving cerebral blood flow state. Cortical perfusion of all rats were lower.4 The results of hypothalamic neurotransmitters indicates the level of NE、DOPA、 5-HT、5-HIAA in model group at 14,18 weeks of age, and DA in 14 weeks of age, E in weeks of age was significantly higher than that in normal group(P<0.05). The level of DA、DOPAC、 5-HT、5-HIA in model group at 14,18 weeks of age was higher than that in non-model group(P>0.05).Sancao Jiangya Decoction reduced the levels of NE. The concentration of DA, DOPAC, 5-HT,5-HIAA had no statistical significance difference compared with model group (P>0.05). Sancao Jiangya Decoction may reduce blood pressure by decreasing NE content in hypothalamus.Conclusion:1 Establish the animal model of hypertension with liver fire hyperactivity syndrome. According to the comprehensive analysis of the three aspects-macro characterization, micro physicochemical indexes, prescription disproof at various levels, the syndrome time window of hypertension with liver fire hyperactivity syndrome was determined.2 Finding the central control area of hypertension hyperactivity of liver fire syndrome preliminary with resting state BOLD. Cardiovascular center is widely distributed in the central nerve system, Functional magnetic resonance imaging analysis of hypertensive rats with hyperactivity of liver fire syndrom showed the activie brain region is concentrated in the central part of the cardiovascular regulation, including hypothalamus preoptic region, hypothalamus tuberal region hypothalamus supraoptic region, hippocampus, midbrain periaqueductal gray matter, tegmentum of pons promote the occurrence and development of high blood pressure and hyperactivity of liver fire syndrome; and the areas such as hippocampus, hypothalamus, periaqueductal gray region is related to emotion and behavior. Hyperactivity liver fire could not store blood and control dispersion, people with this symptom usually show emotional irritability, headaches and dizziness, the activation of these areas can initially explain liver fire hyperactivity, suggesting the direction of the research on biology mechanism of hypertension with hyperactivity of liver fire.3 ASL reveals the state of cerebral blood flow of hypertensive hyperactivity of liver fire syndrome. CBF of rats in each group were decreased with age increased. Cerebral circulation disorder gradually increased.4 Hypothalamus neurotransmitters played a role in hypertension hyperactivity of liver fire syndrome. The NE of model group maintained at a high level, Sancao Jiangya Decoction reduced the levels of NE, showed that in hypothalamus the increase of NE may associate with hypertension hyperactivity of liver fire syndrome. The central nervous mechanisms of hypertension with liver fire hyperactivity syndrom may be related to the regulation of the hypothalamic pituitary adrenal axis (HPA).