RESUMO
ObjectiveTo observe the effects of modified Chaihu Shugansan（CHSG） and its disassembled formulas on angiotensin-converting enzyme 2 （ACE2）-angiotensin （Ⅰ-Ⅶ） ［Ang （Ⅰ-Ⅶ）］-mitochondrial assembly receptor （MasR） axis in hyperlipidemic rats with myocardial ischemia and depression， and to explore the underlying mechanism of its prevention and treatment of myocardial ischemia and depression. MethodA total of 108 male SD rats were randomly divided into a normal group， a model group， a modified CHSG group （11.7 g·kg-1）， a Quyu Huatan disassembled formula group （4.05 g·kg-1）， a Shugan Xingqi disassembled formula group （3.15 g·kg-1）， a Jianpi Yangxue disassembled formula group （4.5 g·kg-1）， a fluoxetine group （0.001 8 g·kg-1）， a trimetazidine group （0.005 4 g·kg-1）， and a simvastatin group （0.001 8 g·kg-1）， with 12 rats in each group. The hyperlipidemia model with myocardial ischemia and depression was induced with a high-fat diet combined with injection of isoproterenol （ISO） and chronic unpredictable mild stress （CUMS） in rats in the model group and groups with drug intervention for eight weeks. The rats in each group with drug intervention were treated correspondingly by gavage from the first day of modeling， while those in the normal group and the model group received the same amount of normal saline. The behavioral changes of rats in each group were observed by open field test and forced swimming test. Left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） were measured by echocardiography. The serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected by the enzyme-labeled apparatus. Hematoxylin-eosin （HE） staining was used to observe the histomorphological changes of the heart. The serum levels of angiotensin Ⅱ （AngⅡ）， ACE2， and Ang（Ⅰ-Ⅶ） were detected by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression of ACE2 and MasR in the hippocampus and the heart was detected by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the model group showed reduced movement time， distance， and average speed in the central area of the open field （P<0.01）， prolonged immobility time of rats in the forced swimming test （P<0.01）， decreased LVFS and LVEF （P<0.01）， inflammatory exudation and disorderly arranged fiber in heart tissues， elevated serum levels of TC， LDL-C， AngⅡ， ACE2 and Ang（Ⅰ-Ⅶ）， diminished HDL-C （P<0.01）， dwindled mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and up-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Compared with the model group， the modified CHSG group displayed increased movement time， distance， and average speed in the center area of the open field （P<0.01）， shortened immobility time in the forced swimming test （P<0.01）， increased LVFS and LVEF （P<0.01）， relieved heart injury， reduced serum levels of TC， LDL-C， AngⅡ， ACE2， and Ang（Ⅰ-Ⅶ）， elevated level of HDL-C （P<0.01）， up-regulated mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and down-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Each disassembled formula could improve the above indexes to a certain extent （P<0.05， P<0.01）， but the effect of the whole formula was optimal. ConclusionThe modified CHSG and its disassembled formulas have the effects of resisting depression， improving myocardial injury， and reducing blood lipid. Due to the synergistic effects of stasis-resolving/phlegm-eliminating drugs， liver-smoothing/Qi-moving drugs， and spleen-tonifying/blood-nourishing drugs in the formula， the modified CHSG is superior to each disassembled formula in efficacy. Its mechanism may be related to the activation of the ACE2-Ang （Ⅰ-Ⅶ）-MasR axis.
RESUMO
<p><b>BACKGROUND</b>Cervicogenic headache (CEH) is caused by a structural abnormality in the cervical spine. Available treatments for CEH include medical therapy, local botulinum toxin injection, cervical epidural corticosteroid injection, and surgery. The objective of this study was to investigate the safety and efficacy of a continuous epidural block of the cervical vertebra.</p><p><b>METHODS</b>Medical records were retrospectively analyzed for 37 patients diagnosed with CEH treated by a continuous epidural block of the cervical vertebra with lidocaine, dexamethasone, and saline (5 ml/min) for 3 - 4 weeks and triamcinolone acetonide 5 mg once weekly for 3 - 4 weeks. Pain was measured via the visual analogue scale (VAS) in combination with quality of life assessment. Outcome measures were patient-reported days with mild or moderate pain, occurrence of severe pain, and the daily oral dosages of non-steroidal anti-inflammatory drug use (NSAID).</p><p><b>RESULTS</b>In the 3 months immediately preceding placement of the epidural catheter, the mean number of days with mild or moderate pain was 22.0 +/- 4.3. The mean occurrence of severe pain was (3.20 +/- 0.75) times and the mean oral dosage of NSAID was (1267 +/- 325) mg. During the first 6 months after epidural administration of lidocaine and corticosteroids, the mean number of days with mild or moderate pain, the mean occurrence of severe pain, and the mean daily oral dosages of NSAIDs were significantly decreased compared to 3-month period immediately preceding treatment (P < 0.01). By 12 months post-treatment, no significant difference in these three outcome measures was noted.</p><p><b>CONCLUSIONS</b>Continuous epidural block of the cervical vertebra for patients with CEH is effective for at least six months. Further research is needed to elucidate mechanisms of action and to prolong this effect.</p>