OBJECTIVE: To investigate the effects of diethylhexyl phthalate (DEHP) exposure on anxiety-like behaviors and learning and memory ability in mice and explore the underlying mechanism. METHODS: Forty male ICR mice were randomized equally into control group (0 mg/kg) and 10, 50 and 100 mg/kg DEHP exposure groups, in which the mice were exposed to DEHP at the indicated doses by gavage for 4 weeks. After the treatments, the mice were assessed for behavioral changes using open filed test, elevated plus-maze and Morris water maze test. Brain tissues were collected from the mice for determination of malondialdehyde (MDA) content, pathologies and expressions of ZO-1 and occludin in the hippocampus. RESULTS: Compared with the control group, the mice with DEHP exposure for 4 weeks exhibited no significant body weight change (P>0.05) but presented with obvious behavioral changes, manifested by reduced movement distance (P < 0.05) and time spent in the center of the open field (P < 0.05), reduced movement distance (P < 0.05) and time spent in the open arm of the elevated maze (P < 0.05), significantly increased latency of searching for the platform (P < 0.05), and decreased frequency of crossing the platform (P < 0.05). HE staining showed obvious vertebral cell death in the hippocampal CA1 to CA3 regions of the mice with DEHP exposure. The exposed mice showed significantly increased MDA content and decreased expressions of ZO-1 and occludin at both the mRNA and protein levels in the hippocampus (P < 0.05 or 0.01). Multivariate linear regression analysis suggested a close correlation between anxiety-like behaviors and learning and memory abilities in DEHP-exposed mice. CONCLUSION DEHP exposure may cause damages of the blood-brain barrier and the pyramidal cells in the hippocampus of mice, thereby inducing anxiety-like behaviors and learning and memory impairment.
Animals ; Anxiety/chemically induced* ; Blood-Brain Barrier/metabolism* ; Diethylhexyl Phthalate/toxicity* ; Male ; Maze Learning ; Mice ; Mice, Inbred ICR ; Occludin/pharmacology*

OBJECTIVETo observe the therapeutic effect of calming the liver and restraining the Yang formula in treating patients with mild or moderate degree of essential hypertension (syndrome of hyperactivity of liver-Yang), and to explore its mechanism in lowering blood pressure.

METHODThe 348 patients with EH of stage I , II were randomly divided into two groups, the 174 patients in the treated group were treated with the calming the liver and restraining the Yang formula, and the 174 patients in the control group were treated with amlodipine. The treatment course for them all was 12 weeks. The related clincial symptoms score and quality of life score estimated before and after treatment at 4th week, 8th week and 12th week were observed. Before and after treatment, the ambulatory blood pressure (AMBP), heart rate, blood lipid, serum livels of high-sensitivity C-reactive protein (Hs-CRP), Angiotensin-II (Ang II) and calcitonin gene-related peptide (CGRP) were measured respectively in 40 patients of the treared group and 40 patients of the control group.

RESULTAfter treatment, the treatment in the treated group showed an effect better than that in the control group in terms of nigh-time blood pressure reducing rate (P < 0.05). The reducing blood pressure variability and total effective rate in the treated group were no significant than that in the control group. In respect of reducing symptomatic scores on dizzy, soreness and weakness of the waist and knees, disturbed and dry and bitter of mouth, ameliorating quality of life score, decreasing the levels of heart rate, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol(HDL-C) in the treated group were showing marked improvement as compared with that in the control group (P < 0.05 or P < 0.1). The improvement in the level of Ang II , Hs-CRP and CGRP before treatment in two groups were more significant than that after treatment (P < 0.05). However There were no difference in after treatment between the treated group and the control group.

CONCLUSIONThe calming the liver and restraining the Yang formula shows favorable efficacy in lowering blood pressure on the patients with mild or moderate degree of essential hypertension. It can reduce the clincial symptoms, improve the quality of life, regulate blood lipid metabolism. Its mechanism may be related to the functional relieving inflammatory reaction and inhibition the activity of renin-angiotensin-aldosterone system (RAAS).

Adult ; Aged ; Amlodipine ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Anxiety ; chemically induced ; physiopathology ; Blood Pressure ; drug effects ; Cholesterol ; metabolism ; Cholesterol, HDL ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Triglycerides ; metabolism