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ObjectiveTo observe and compare the electrocardiogram index， myocardial morphology， and connexin 43 （Cx43） expression of two rat models of acute cerebral infarction （ACI） due to stasis combined with toxin complicated with cerebral-cardiac syndrome （CCS）， and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups （n=10）： normal ， syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast （CA/Y）， multi-infarct induced by micro-embolism （ME）， middle cerebral artery occlusion （MCAO）， CA/Y+ME， and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan （CA） at 10 mg·kg-1 on the first day and subcutaneous injection with dry yeast （Y） suspension （2 mg·kg-1） on the second day of modeling. Twenty-four hours after the modeling of ACI， the electrocardiograms （ECGs） of rats in each group were collected and the number/percentage （%） of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and myocardial injury was assessed by hematoxylin-eosin （HE） staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group， CA/Y+MCAO group had the highest rate of abnormal ECG （P<0.01）. Compared with the normal， CA/Y， ME， and CA/Y+ME groups， the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave， shortened P-R interval， and extended Q-T interval， which were particularly obvious in the CA/Y+MCAO group （P<0.05， P<0.01） and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups， especially in the CA/Y+MCAO group （P<0.01）. ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover， the CA/Y+MCAO method has higher abnormal electrocardiogram rate， severer myocardial pathological injury， and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.
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ObjectiveTo screen and establish animal models of combined stasis and toxin syndrome based on the comparison of three modeling methods， i.e.， carrageenan （Ca）， Ca combined with dried yeast （Ca+Yeast）， and Ca combined with lipopolysaccharide （Ca+LPS）. MethodForty SPF male SD rats were randomly divided into normal group， Ca group， Ca+Yeast group， and Ca+LPS group， with 10 rats in each group. The Ca group， Ca+Yeast group， and Ca+LPS group received an intraperitoneal injection of Ca （10 mg·kg-1） on the first day. The Ca+LPS group received an intraperitoneal injection of LPS （50 μg·kg-1） on the second day， and the Ca+Yeast group received a subcutaneous injection of dry yeast suspension （2 mg·kg-1） on the back on the second day. The rectal temperature of each group was dynamically observed after modeling. After 24 hours of modeling， the macroscopic evaluation indexes， including tongue manifestation， pulse， and black tail length in each group were observed. The PeriCam PSI imaging system was used to detect the blood flow perfusion of the rat tail. The automatic hemorheology analyzer was used to measure the whole blood viscosity and plasma viscosity of each group. The PL platelet function analyzer was used to detect the platelet aggregation rate of the rats. The enzyme-linked immunosorbent assay （ELISA） was used to detect the interleukin-6 （IL-6） level in the rat plasma. The myocardial tissue， brain tissue， and lung tissue of each group of rats were observed by hematoxylin-eosin （HE） staining. ResultCompared with the normal group， all three model groups showed varying degrees of black tail （P<0.05， P<0.01）， reduced blood flow perfusion at the tail end （P<0.05， P<0.01）， decreased R， G， and B values of tongue manifestation （P<0.05， P<0.01）， and increased maximum platelet aggregation rate （P<0.05， P<0.01）. The pulse amplitudes of the Ca+Yeast group and the Ca+LPS group were lower than that of the normal group （P<0.05， P<0.01）. In addition， the average rectal temperature of the Ca+Yeast group increased after 24 hours of modeling （P<0.01）， and the low-， medium-， and high-shear whole blood viscosity and plasma viscosity increased （P<0.05， P<0.01） as compared with those in the normal group. Additionally， the expression level of the plasma inflammatory factor IL-6 was significantly up-regulated （P<0.05）. Pathological morphology results showed that the Ca+Yeast group had the most severe pathological changes， with small foci of myocardial fiber dissolution， inflammatory cell infiltration， and fibroblast proliferation observed. In the hippocampal area， the neurons were sparse and had undergone red degeneration. In the small focus of the lung interstitium， lymphocytes and neutrophils were infiltrated. ConclusionThe animal model of combined stasis and toxin syndrome was properly established using Ca+Yeast. The systematic evaluation system of the model， which includes traditional Chinese medicine four diagnostic information， western medicine microscopic indicators， and tissue pathological morphology， is worthy of consideration and reference by researchers.
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Objective:To observe the effect of Lingshao-Zaoren Decoction on urodynamics and the expression of Piezo1 if overactive bladder (OAB) rats. Methods:Thirty SPF grade female SD rats were randomly divided into blank group, model group, Tolterodine control group, low-dose and high-dose Lingshao-Zaoren Decoction groups, with 6 rats in each group. The OAB rats were modeled by intraperitoneal injection of Cyclophosphamide. After the successful modeling, Tolterodine control group was given 0.36 mg/kg Tolterodine tartrate, the low-dose and high-dose Lingshao-Zaoren Decoction groups were given 1.59 and 3.18 g/kg Lingshao-Zaoren Mianjian granules by gavage, the blank group and model group were given the same amount of distilled water, once a day for 14 days. After 14 days, the urodynamics of rats in each group were detected. The bladder volume and maximum bladder pressure were observed respectively. The pathological changes of bladder tissue were observed by HE staining. The expression of Piezo1 protein in bladder tissue was detected by immunohistochemistry and Western blot. The expression of Piezo1 mRNA in bladder tissue was detected by qPCR. Results:Compared with the blank group, the body weight, bladder volume and maximum bladder pressure of the model group were significantly reduced ( P<0.01). HE staining result showed that the model group had hyperplasia of urinary tract epithelium, degeneration, necrosis and abscission of epithelial cells, infiltration of a large number of inflammatory cells in stroma, vascular proliferation, thickening of vascular wall, hyperplasia of mucosal smooth muscle, disorder of arrangement, and significant up regulation of Piezo1 protein expression ( P<0.01). Compared with the model group, the weight [(244.83 ± 6.05) g, (233.33 ± 11.76) g vs. (219.00 ± 9.70) g] of rats in the Tolterodine control group and high-dose group of Lingshao-Zaoren Decoction significantly increased ( P<0.01), and the bladder volume [(0.93 ± 0.31) ml, (1.17 ± 0.17) ml, (1.21 ± 0.23) ml vs. (0.50 ± 0.16) ml] and maximum bladder pressure [(42.00 ± 3.03) cmH 2O, (45.83 ± 7.19) cmH 2O, (46.83 ± 8.23) cmH 2O vs. (30.50 ± 5.47) cmH 2O] of rats in the Tolterodine control group, low-dose and high-dose Lingshao-Zaoren Decoction groups were significantly increased ( P<0.01); the bladder epithelial hyperplasia and degeneration degree, interstitial inflammatory cell infiltration degree and vascular hyperplasia degree of rats in the Tolterodine control group, low-dose and high-dose Lingshao-Zaoren Decoction groups significantly increased. The expression of Piezo1 mRNA (1.50 ± 0.04, 2.05 ± 0.08, 1.44 ± 0.10 vs. 2.56 ± 0.11) and protein in the Tolterodine control group, low-dose and high-dose Lingshao-Zaoren Decoction groups were significantly decreased ( P<0.01). Conclusion:Lingshao-Zaoren Decoction can increase the bladder volume and maximum bladder pressure of urinary incontinence caused by detrusor overactivity in rats with overactive bladder, which may be related to reduction of Piezo1 expression.
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This study was aimed to observe behavioral changes of post-stroke depression (PSD) rats, and to assess effect ofJie-Du Tong-Luo(JDTL) capsule onqi-supplementing and depression-relieving. Microspheres were injected from external carotid artery of rats under anesthesia to prepare the multiple cerebral infarction. Aftermid long term feeding, PSD rat model was established. Then, open-field test (OFT), tail suspension test (TST), forced swimming test (FST) and glucose preference test were employed to study behavioral changes of rats. The results showed that rats suffered multiple cerebral infarction after mid long term feeding formed PSD, which were indicated by reduced food consume, slow body weight increasing, reduction of spontaneous movement and inquiry activity, prolonged accumulative immobility time in TST, FST and lowered glucose preference, compared with rats in the normal group. Compared with the model group, rats in the JDTL capsule group andBu-Chang Xin-Nao-Tonggroup showed larger body weight increase, higher scores in OFT, reduced immobility time in TST, FST, and elevated glucose preference. It was concluded that JDTL capsule had significant efficacy on rats’ body weight, behavior and glucose preference, which might be its pharmacological basis onqi-supplementing and depression-relieving.
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This study was aimed to observe the effect ofRong-Shuan (RS) capsule on rodent tolerance against cerebral ischemia, hypoxia and cerebral reserve capacity, which was related to promote blood circulation and remove blood stasis. Acute cerebral ischemia and anoxia models were established by permanent left carotid artery ligation on C57 BL/6 mice and hypoxia inhalation (O2?N2 = 8?92) for 15 min. Duodenal administration of RS capsule at different doses (100, 200 or 400 mg·kg-1) or saline were given 10 min after ischemia onset. The local brain blood circulation changes and neurobehavioral function were evaluated 24 h after ischemia onset. SD rats were given RS capsule at different doses (75, 150, 300 mg·kg-1) or saline. The effect of RS capsule on improvement of microcirculation disturbance induced by high molecular dextran was observed. The results showed that compared with the sham operation group, the brain blood circulation in the model group was significantly decreased; the cerebral infarction area increased; and the behavioral score after cerebral hypoxia was significantly increased (P < 0.05, orP < 0.01). Meanwhile, after the injection of high molecular dextran among rats in the model group, the cerebral leptomeninx microcirculation was obviously slowed down at 3 timepoints, which were 10, 20 and 30 min. Compared with the model group, RS capsule (400 mg·kg-1) can significantly increase the local blood circulation in the brain of mice, improve behavioral disturbance, reduce cerebral ischemia area (P< 0.05, orP < 0.01). RS capsule can also improve blood flow velocity and flow pattern in cerebral leptomeninx microcirculation disturbance induced by high molecular dextran at different timepoints (P < 0.05, orP < 0.01). It was concluded that RS capsule can increase the tolerance against cerebral ischemia, hypoxia and cerebral reserve capacity in order to protect the neural tissues to promote neuronal recovery.
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The rat model of multi-infarct was adopted in this study to elucidate the protective mechanism of Sailuotong capsule (Sailuotong) in recovery period of multiple cerebral infarction. The effects of Sailuotong on levels of Glu, GABA and the expression of NMDA receptor subtypes including NR1, NR2A and NR2B, were detected. The multi-infarct model rats were established by injecting embolizing microsphere via internal carotid artery, and were given Sailuotong treatment (16.5 and 33.0 mg x kg(-1)) for 60 days. The pathological changes in brain ultrastructure were observed by transmission electron microscope. The levels of Glu and GABA in brain tissue were measured with high performance liquid chromatography. The expression of NMDA receptors including NR1, NR2A and NR2B in neurons was evaluated by immunohistochemical staining. Compared with the sham rats, abnormal changes were observed in ultrastructures of neurons, neuroglia cells and synapses of model rat brains. Moreover, significant decrease of Glu and GABA, as well as the elevated expression of NR1, NR2A and NR2B were detected in brain tissues. Sailuotong (16.5 and 33.0 mg x kg(-1)) could improve ultrastructure of cerebral tissue, facilitate synthesis of Glu and GABA, and down-regulate expression of NR1, NR2A and NR2B in neurons. The results demonstrated that Sailuotong could exert neuroprotective effects to some extent in the recovery phase of multiple cerebral infarction by promoting expression of NMDA receptors and synthesis of Glu and GABA.
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Background: Isolated systolic hypertension (ISH) is a common disease in elderly people, threatening their health. Traditional Chinese medicine (TCM) treatment or integrative treatment had advantages in improving quality of life and protecting target organs, but need to be proved by large evidence-based researches. Objective: To observe the effects of TCM treatment (Jiangya Capsule) or integrative treatment (combination of Jiangya Capsule and nimodipine) on blood pressure and vasoactive agents, and their safety in elderly ISH patients. Design, setting, participants and interventions: A multicenter, randomized, double-blind controlled trial was adopted. A total of 270 elderly ISH patients recruited from Xiyuan Hospital, and TCM Hospital and Community Health Service Centers of Yanqing County of Beijing were randomly divided into 3 groups: TCM group (Jiangya Capsule plus nimodipine simulation, 90 cases), integrative group (Jiangya Capsule plus nimodipine, 90 cases) and Western medicine (WM) group (nimodipine plus Jiangya Capsule simulation, 90 cases). They were all treated for 4 weeks. Main outcome measures: Before and after 4-week treatment, office blood pressure, 24-hour ambulatory blood pressure, serum nitric oxide (NO), and plasma endothelin-1 (ET-1), thromboxane B2 (TXB2) and 6-keto-prostaglandin 1alpha (6-keto-PGF1alpha) were detected, and safety evaluation was conducted. Results: After 4-week treatment, 5 patients in TCM group were lost to follow-up and another 5 patients were excluded, and 80 patients finished the trial; 7 patients in integrative group were lost to follow-up and another 7 patients were excluded, and 76 patients finished the trial; 2 patients in WM group were lost to follow-up and another 3 patients were excluded, and 85 patients finished the trial. After treatment, systolic blood pressure (SBP) decreased in each group (P<0.05), and integrative treatment was superior to TCM or WM treatment in decreasing SBP (P<0.05). Twenty-four hour average SBP and day average SBP decreased significantly in each group, and night average SBP decreased in integrative group, and integrative treatment was superior to TCM or WM treatment in decreasing day average SBP. Serum NO and plasma 6-keto-PGF1alpha levels were elevated and plasma ET-1 and TXB(2) levels were reduced after treatment, and integrative treatment was superior to TCM or WM treatment in reducing plasma TXB(2) level. Conclusion: TCM treatment or integrative treatment has affirmative effects and safety in treating elderly ISH patients, and integrative treatment has superiority in improving some indexes, and deserves further study.
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<p><b>OBJECTIVE</b>To observe the intervention effects of Huannao Yicong decoction on cognitive function and apoptosis and expression of relative regulative gene of Hippocampus in cognitive impairment rats induced by complex factors.</p><p><b>METHOD</b>60 SD rats were divided randomly into Huannao Yicong decoction high-dose group (HHG), Huannao Yicong decoction low-dose group (HLG), positive control group (PCG), model control group (MCG) and blank control group (BCG). Rats in the BCG were received daily hypodermic injection of tales doses of normal sodium for 10 weeks with normal feeder. Rats in other groups were received daily hypodermic injection of D-galactose with the concentration of 50 mg kg(-1) for 10 weeks, from the 5th week on, half fat feeder were fed until the end of the 10th week. From the 7th on, rats in HHG were administered with 0.01 mL g(-1) Huannao Yicong decoction suspension by gavage (crude drug 14 g kg(-1)). Rats in LHG were administered with 0.01 mL g(-1) Huannao Yicong decoction suspension by gavage (crude drug 7 g kg(-1)). Rats in PCG were administered with 0.01 mL g(-1) hydrochloricdonepezil suspension by gavage (0.4 mg kg(-1)). Rats in MCG and BCG were administered with 0.01 mL g(-1) distilled water by gavage, intragastric administration was given daily until the end of the 10th week. The behaviors of the rats were observed by morris water maze, the apoptosis and expression of relative regulative gene of hippocampus were measured.</p><p><b>RESULT</b>The morris water maze indicated that compared with the BCG, the platform locating latency of rats in the MCG was longer and the frequency of swimming through the platform was fewer(P <0.05, P < 0.01), compared with the MCG, there was significant difference on the frequency of swimming through the platform in the HHG and PCG (P <0.05, P <0.01). The number of apoptosis cells in the MCG was more than that in the BCG, the difference was significant (P <0.01), the number of apoptosis cells in the HHG, HLG and PCG was reduced and the ratio of Bcl-2 and Bax was increased (P < 0.01).</p><p><b>CONCLUSION</b>Huannao Yicong decoction could improve the learning and memory functions of cognitive impairment rats, inhibit the apoptosis of cells in hippocampus, regulate the expression of relative gene, accelerate the repairing of cells, protect the impaired brain tissue, and these may be part of the channels of clinical effects.</p>
Subject(s)
Animals , Female , Humans , Rats , Apoptosis , Cognition Disorders , Drug Therapy , Genetics , Metabolism , Disease Models, Animal , Drugs, Chinese Herbal , Gene Expression , Hippocampus , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Genetics , Metabolism , Random Allocation , Rats, Sprague-Dawley , bcl-2-Associated X Protein , Genetics , MetabolismABSTRACT
OBJECTIVE: To observe the effect and explore the mechanism of Huannao Yicong capsule in treating senile patients with mild cognitive impairment (MCI). METHODS: The investigational drugs were packed by blind method. A randomized, double-blind and controlled trial was conducted on ninety senile patients with MCI. Other forty-five senile healthy persons were recruited to the healthy control group. The ninety senile patients were randomly divided into the Huannao Yicong capsule-treated group (45 patients administered with three Huannao Yicong capsules and two aniracetam capsule analogues) and aniracetam-treated group (45 patients treated with two aniracetam capsules and three Huannao Yicong capsule analogues). Patients in the two groups were treated three times daily for 16 weeks. Memory, traditional Chinese medicine syndrome, cerebral blood flow, free radicals and inflammatory mediators, such as superoxide dismutase (SOD), malondialdehyde (MDA), acetylcholinesterase (AchE), interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) were determined before and after the treatment. Blood lipids, including triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B-100 (ApoB-100), were detected before and after the treatment. The safety indexes, such as routine tests of blood and urine, hepatic and renal function tests and electrocardiogram (ECG) were taken before and after the treatment. RESULTS: Index score of clinical memory scale in senile healthy people was significantly higher than that in MCI patients before treatment (P<0.01), and the content of AchE, IL-1alpha and IL-6 was obviously lower (P<0.01, P<0.05), the activity of SOD was higher (P<0.05). No significant difference was found in direction memory of clinical memory scale between the two treatment groups. Other index scores of clinical memory scale and traditional Chinese medicine syndrome in patients of Huannao Yicong capsule-treated group were significantly improved as compared with those of the aniracetam-treated group (P<0.05, P<0.01). The blood flow parameters of anterior cerebral artery, posterior cerebral artery and resistant index in patients of Huannao Yicong capsule-treated group were increased significantly (P<0.01, P<0.05). Huannao Yicong capsule could significantly increase the activity of serum SOD and decrease the content of AchE, IL-1alpha and IL-6 (P<0.01, P<0.05), better than aniracetam. Furthermore, Huannao Yicong capsule could significantly improve the blood lipid, such as the level of TG, LDL-C, HDL-C, ApoA-1 and ApoB-100 (P<0.01, P<0.05), and better than aniracetam (P<0.01, P<0.05). No significant changes were found after treatment in safety indexes, such as routine tests of blood and urine, hepatic and renal function tests and ECG. CONCLUSION: Huannao Yicong capsule has better therapeutic effect than aniracetam capsule in treating senile mild cognitive impairment.
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Brain slice technique has been widely applied in the field of neuroscience.This article reviews the application of brain slice in anti-cerebral ischemia pharmacology research on electrophysiology,synaptic plasticity,pathomorphology,neurotransmitters and in the field of Chinese medicine.
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Objective To study the correlation between senile mild cognitive impairment (MCI) and metabolize of oxygen-derived free radicals, acetylcholinesterase(AchE), blood lipids and inflammatory mediator. Methods Memory,the levels of superoxide dismutase (SOD), malondialdehyde (MDA), AchE, blood lipids, IL-1? and IL-6 of MIC group(45 cases) and elder healthy group(45 controls) were measured, funther compare and correlative analysis were made.Results Compared with elder healthy group, memory score in each item and memory quotient in MCI group were significantly lower (allP