Clinical Effects of Xingshen Tongqiao Huoxue Decoction in Treatment of Dysphagia Caused by Cricopharyngeal Achalasia After Stroke / 中国实验方剂学杂志

Objective:To explore the clinical effects of Xingshen Tongqiao Huoxue decoction in the treatment of dysphagia caused by cricopharyngeal achalasia （CPA） after cerebral infarction and its influence on neurotransmitters. Method:One hundred and fourteen eligible patients were randomly divided into a control group （56 cases） and a treatment group （58 cases）. Patients in both groups received balloon catheter dilatation and rehabilitation training. In the observation group， the Tiandan Tongluo capsules were further orally taken， five capsales per time， three times per day. In the control group， the Xingshen Tongqiao Huoxue decoction was provided， one dose per day. The treatment lasted for four weeks. Following the videofluoroscopic swallow study （VFSS） and water-swallowing test （WST） before and after treatment， the swallowing quality of life questionnaire （SWAL-QOL）， functional oral intake scale （FOIS） and National Institutes of Health Stroke Scale （NIHSS） scores were calculated. The serum brain-derived neurotrophic factor （BDNF）， substance P （SP）， dopamine （DA）， 5-hydroxytryptamine （5-HT） and nerve growth factor （NGF） levels before and after treatment were detected， and the complications were recorded. Result:The clinical efficacy of the treatment group was superior to that of the control group （<italic>Z</italic>=2.079， <italic>P</italic><0.05）. Both VFSS and WST findings in the treatment group were milder than those in the control group （<italic>Z</italic>=2.004， <italic>P</italic><0.05 and <italic>Z</italic>=1.973， <italic>P</italic><0.05）. The VFSS， SWAL-QOL， and FOIS scores and the BDNF， DA， SP， 5-HT and NGF levels of the treatment group were elevated in contrast to those of the control group （<italic>P</italic><0.01）， whereas the NIHSS score declined （<italic>P</italic><0.01）. The complication rate in the treatment group was （8/58） 13.79%， significantly lower than （17/56） 30.36% in the control group （<italic>χ</italic>²=4.565， <italic>P</italic><0.05）. Conclusion:On the basis of balloon catheter dilatation and rehabilitation training， the Xingshen Tongqiao Huoxue decoction can significantly enhance the swallowing function， improve the quality of life， and reduce complications in patients with dysphagia caused by CPA after cerebral stroke.

Tongqiao Huoxuetang Improves Neurological Deficits in CIRI Rats by Regulating Glu-Gln Circulation to Reduce Glutamate Excitotoxicity of Astrocytes / 中国实验方剂学杂志

Objective:To observe and compare the protective effects of Tongqiao Huoxue decoction （TQHX） prepared by three methods against cerebral ischemia-reperfusion injury （CIRI）， and to explore its mechanism through the glutamate （Glu） metabolic pathway in astrocytes. Method:The male SD rats of SPF grade were subjected to CIRI model induction by the modified middle cerebral artery occlusion method. The model rats were randomly divided into a model group， a sham operation group， and water-decocted， wine-decocted， and alcohol-extracted TQHX （6.3 g·kg^-1·d^-1） groups. The rats were treated correspondingly for 7 days. Those in the sham operation group and the model group were treated with an equal volume of normal saline by gavage. After the final treatment， the neurological function of rats was assessed by the modified neurological severity score （mNSS）. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of ischemic brain tissues in rats. High-performance liquid chromatography （HPLC） was used to detect glutamate （Glu） in ischemic brain tissues. The expression of glutamate transporter-1 （GLT-1） and glial fibrillary acidic protein （GFAP） and co-expression of glutamine synthetase （GS） and GFAP in ischemic brain tissues were detected by immunofluorescence assay. Western blot was used to detect the protein expression of GFAP， GLT-1， and GS. Result:Compared with the sham operation group， the model group showed increased mNSS （<italic>P</italic><0.01）， large necrosis of cerebral cortex in ischemic brain tissues with disordered cell arrangement， obscure boundary， intracellular edema， and inflammatory infiltration， elevated Glu in ischemic brain tissues （<italic>P</italic><0.01）， declining GLT-1-GFAP co-expression and GS-GFAP co-expression （<italic>P</italic><0.01）， up-regulated expression of GFAP protein， and reduced protein expression of GLT-1 and GS（<italic>P<</italic>0.05，<italic>P<</italic>0.01）. Compared with the model group， the TQHX groups showed decreased mNSS （<italic>P<</italic>0.01）， relieved injury in the cerebral cortex and hippocampal nerve cells in ischemic brain tissues， reduced Glu expression（<italic>P<</italic>0.05，<italic>P<</italic>0.01）， elevated co-expression of GLT-1 and GFAP （<italic>P<</italic>0.05，<italic>P<</italic>0.01）， and up-regulated protein expression of GFAP and GLT-1（<italic>P<</italic>0.05，<italic>P<</italic>0.01）. The co-expression of GS and GFAP （<italic>P<</italic>0.05，<italic>P<</italic>0.01）and the expression of GS （<italic>P<</italic>0.01）were increased in the wine-decocted and alcohol-extracted TQHX groups. Compared with the water-decocted TQHX group， the alcohol-extracted group showed increased GLT-1-GFAP and GS-GFAP co-expression（<italic>P<</italic>0.05）； the wine-decocted and alcohol-extracted TQHX groups exhibited elevated GS protein expression （<italic>P<</italic>0.05）； the alcohol-extracted TQHX group displayed declining Glu content （<italic>P</italic><0.01） and increased protein expression of GFAP and GLT-1 （<italic>P<</italic>0.05， <italic>P<</italic>0.01）. Compared with the wine-decocted TQHX group， the alcohol-extracted TQHX group showed increased protein expression of GFAP and GLT-1（<italic>P<</italic>0.05，<italic>P<</italic>0.01）. Conclusion:TQHX prepared by three methods can improve neurological deficits in CIRI rats. The effect is presumedly achieved by promoting the further activation of astrocytes， increasing the expression of GLT-1 and GS， promoting the clearance of Glu accumulated in the synaptic cleft by astrocytes through the Glu-glutamine （Gln） circulation， and reducing the excitotoxicity of Glu. The alcohol-extracted TQHX group was superior to the water-decocted and wine-decocted TQHX groups in reducing the content of Glu in ischemic brain tissues， promoting the activation of astrocytes， and enhancing the protein expression of GLT-1 and GS.

Clinical research of Tongqiao-Huoxue decoction for the treatment of vertebrobasilar artery insufficiency vertigo with stasis orifice type / 国际中医中药杂志

Objective To investigate the clinical application of Tongqiao-Huoxue decoction for the treatment of vertebrobasilar artery insufficiency vertigo with stasis orifice type. Methods According to the random table method, 93 vertebrobasilar artery insufficiency vertigo patients with stasis orifice type were divided into the control group (n=46) and the treatment group (n=47). The patients in the control group were treated with fluoguizine hydrochloride, while the patients in the treatment group were treated with Tongqiao-Huoxue decoction on the basis of control group. Two groups were treated for 4 weeks. The clinical total effective rate of two groups of patients after treatment was compared. The LVA mean blood flow velocity, RVA mean blood flow velocity, BA mean blood flow velocity, total blood viscosity, plasma viscosity, erythrocyte aggregation index, fibrinogen, TC, TG, LDL-C and HDL-C were detected respectively before and after treatment. In addition, the adverse reaction incidence of two groups of patients were observed. Results The total effective rate of treatment group was 93.6% (44/47), while the total effective rate of control group was 78.3% (36/46). The difference between two groups was statistically significant (χ2=4.559, P=0.033). After treatment,the LVA mean blood flow velocity (38.34 ± 3.72 cm/s vs. 29.73 ± 3.11 cm/s, t=12.096), RVA mean blood flow velocity (41.12 ± 4.05 cm/s vs. 34.11 ± 3.86 cm/s, t=8.541),BA mean blood flow velocity (48.92 ± 5.24 cm/s vs. 40.75 ± 4.63 cm/s, t=7.962), HDL-C (2.13 ± 0.64 mmol/L vs. 1.54 ± 0.53 mmol/L, t=4.836) of treatment group were significantly higher than the control group (P<0.05), while the total blood viscosity, plasma viscosity, erythrocyteaggregation index, fibrinogen, TC, TG, LDL-C of treatment group were significantly lower than the control group (t value were 5.457, 8.875, 3.661, 6.549, 3.838, 6.369, 5.201, all Ps<0.05). No serious adverse reactions occurred during the treatment of the two groups. Conclusions The clinical curative effect of Tongqiao-Huoxue decoction for the treatment of vertebrobasilar artery insufficiency vertigo with stasis orifice type is significantly, and it can increases blood flow to the brain, improve hemorheology and lipid levels. It has the high security of the forward curative effect.

Activity of tongqiao huoxue decoction on the memory and learning ability and fluorescence intensity of intracellular calcium concentration of hippocampal neurons of vascular dementia rats / 中国药学杂志

OBJECTIVE: To study activity of tongqiao huoxue decoction (TQHXD) on memory and learning ability of rats with vascular dementia (VD) and its influence on fluorescence intensity of intracellular calcium concentration of hippocampal neurons. METHODS: Vascular dementia model was established by using improved bilateral carotid artery ligation method. The Morris water maze experiment was adopted to evaluate the ethology of VD rats. The fluorescence intensity of hippocampus intracellular calcium was detected by flow cytometry. RESULTS: Compared with the model group, high, middle and low dose group of TQHXD significantly reduce the time of escape latency and the distance of climbing on the platform (P < 0.01). The entries in the second quadrant, the times in the second quadrant and the distance in the second quadrant in relation to high, middle and low dose groups of TQHXD were increasing significantly (P < 0.05) and the latency to first entry in the second quadrant was shorten (P < 0.05). The fluorescence intensity of intracellular calcium in hippocampal neurons of the high, middle and low dose groups of TQHXD was lower than that of the model group (P < 0.01, P < 0.05). CONCLUSION: TQHXD can improve the memory and learning ability of rats with VD significantly. The mechanism may be related to reduce the intracellular calcium concentration in the hippocampus, thereby the damage of nerve cells is reduced.

Tongqiao Huoxue Decoction ameliorates learning and memory defects in rats with vascular dementia by up-regulating the Ca(2+)-CaMKII-CREB pathway / 中国天然药物

The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.

The regulatory effect of Tongqiao Huoxue decoction on motilin and vasoactive intestinal peptide in rats with cerebral infarction at acute stage / 中国中西医结合急救杂志

Objective To observe the effect of Tongqiao Huoxue decoction on the changes of motilin (MTL) and vasoactive intestinal peptide (VIP) and its protective effect on gastric mucosa in rats with cerebral infarction at acute stage.Methods According to random number table, 96 Wistar rats were divided into six groups: normal control, sham operation, cerebral infarction model, cimetidine, Tongqiao Huoxue decoction routine dose and low dose groups, eachn = 16. Cerebral infarction model group was established by using a suture to ligate the middle cerebral artery, resulting in its occlusion. The rats of cerebral infarction model group and sham operation group were lavaged with 2 mL of normal saline. Tongqiao Huoxue decoction routine dose group was lavaged with 2 mL of Tongqiao Huoxue decoction (1.3 g/mL), while Tongqiao Huoxue decoction low dose group was lavaged with 1 mL of Tongqiao Huoxue decoction (1.3 g/mL) plus 1 mL of normal saline. Cimetidine group was lavaged with cimetidine (0.1 g/kg), and nothing was done for the normal control group. On the 4th and 7th day after the delivery of treatment, inferior vena venous blood samples were collected to detect the plasma MTL and VIP concentrations. Then the gastric tissues were obtained and examined under an electron microscope.Results There were no statistically significant differences between the normal control group and sham operation group in plasma levels of MTL and VIP (bothP > 0.05). The plasma levels of MTL and VIP at 4 days and 7 days after the delivery of treatment in cerebral infarction model group were higher than those in the normal control group and sham operation group [4 days MTL (ng/L): 189.51±13.48 vs. 117.01±11.38, 117.67±12.73, VIP (ng/L): 94.86±4.14 vs. 60.98±5.42, 62.55±6.60, bothP < 0.05; 7 days: MTL (ng/L): 183.05±14.49 vs. 119.79±10.64, 120.27±11.48, VIP (ng/L): 91.92±3.77 vs. 59.63±4.29, 58.10±4.99, bothP < 0.05]. Plasma levels of MTL and VIP in cimetidine group, Tongqiao Huoxue decoction routine dose group and low dose group were significantly lower than those in cerebral infarction model group. Compared with Tongqiao Huoxue decoction low dose group and cimetidine group, the degrees of descent in plasma levels of MTL and VIP were apparently lower on the 7th day in Tongqiao Huoxue decoction routine dose group [MTL (ng/L): 138.72±8.02 vs. 152.16±12.66, 156.60±11.87, bothP < 0.05; VIP (ng/L):68.18±3.41 vs. 81.12±3.98, 78.89±2.13, bothP < 0.05]. The results of electron microscope: compared with normal control group and sham operation group, obvious pathological changes in gastric mucosa in model group were found. In Tongqiao Huoxue decoction routine group, Tongqiao Huoxue decoction low dose group and cimetidine group, the gastric mucosal lesions were milder, and the curative effects of Tongqiao Huoxue decoction routine group were much better.Conclusions During the acute stage of cerebral infarction, significant damage is seen in gastric mucosa in rats. Tongqiao Huoxue decoction not only can effectively regulate the expression levels of MTL and VIP, but also has certain protective effect on gastric mucosa, and its efficacy being directly proportional to the dosage.

A study of Tongqiao Huoxue decoction combined with edaravone and hyperbaric oxygen for treatment of delayed encephalopathy after carbon monoxide poisoning / 中国中西医结合急救杂志

Objective To study the clinical curative effect of Tongqiao Huoxue decoction combined with edaravone and hyperbaric oxygen for treatment of delayed encephalopathy after carbon monoxide poisoning (DEACMP). Methods A prospective study was conducted. Forty-six patients with DEACMP admitted into Yidu Central Hospital of Weifang Medical College from January 2012 to January 2014 were randomly divided into observation group (23 cases) and control group (23 cases). The basic treatments of two groups were identical. Based on the basic treatments including hyperbaric oxygen and citicoline sodium injection etc, the observation group was treated with our-self made Tongqiao Huoxue decoction which could be modified in accord to the individual differentiation of syndromes in traditional Chinese medicine (the composition of decoction included Paeoniae Radix Rubra 15 g, Chuanxiong Rhizoma 15 g, Persicae Semen 15 g, Carthami Flos 15 g, Zingiberis Rhizoma Recens 3 pieces, Jujubae Fructus 2 pieces, Moschus 0.5 g, Allium Fistulosum 1 segment). The decoction was administered orally or by nasogastric gavage, one dosage everyday for 1 month, and in the mean time, edaravone intravenously drip 30 mg was given to the observation group twice a day for 14 days. The control group was given hyperbaric oxygen and other conventional treatment for 30 days. The clinical therapeutic effect and adverse reaction were observed after treatment for 30 days. The changes of intelligent level were detected by Hasegawa dementia scale (HDS), and the changes of latency of P300 were measured by electromyologram/evoked potential instrument in two groups before and after treatment. Results The total effective rate in observation group was significantly higher than that in control group [91.3% (21/23) vs. 65.2% (15/23), P < 0.01]. Elevation of creatinine occurred in 1 case, moderate increase in alanine aminotransferase (ALT) appeared in 1 case, and both of them were reduced to normal after treatment in observation group; no adverse reaction occurred in control group. The HDS scores were significantly higher 30 days after treatment than those before treatment in the two groups [control group:13.4±2.8 vs. 6.8±2.3, observation group:20.8±3.4 vs. 6.6±2.5, both P<0.05]. The latency of P300 after treatment was significantly lower in two groups than that before treatment [control group (ms): 355.7±25.7 vs. 385.5±27.8, observation group (ms): 337.3±24.6 vs. 386.8±25.4, both P < 0.05], the change in observation group being more significant [the HDS score: 20.8±3.4 vs. 13.4±2.8, the latency of P300 (ms): 337.3±24.6 vs. 355.7±25.7, both P<0.05]. Conclusion Tongqiao Huoxue decoction combined with edaravone and hyperbaric oxygen has favorable cognitive effect on patients with DEACMP, thus, it can be used extensively in clinic.

Randomized Controlled Clinical Trial on Efficacy of Chinese Medicine Combined with Electric Acupuncture in the Treatment of Sudden Deafness / 世界科学技术-中医药现代化

This study was aimed to explore the clinical efficacy and differences in hemorheological parameters in sudden deafness treated with Chinese medicine combined with electric acupuncture and western medicine . Patients were selected according to the diagnostic criteria of sudden deafness. Patients were randomly divided into the Chinese medicine combined with electric acupuncture group ( 35 cases ) and the western medicine group (30 cases). In the treatment group, Tongqiao Huoxue Decoction was orally administrated in combination with electric acupuncture on Jiaj i points on the neck region . In the western medicine group , alprostadil and prednisone were used . For both groups , 10 days were one treatment course . The results showed that after two treatment courses , the hearing improvement of two groups was compared . The total efficiency of Chinese medicine combined with electric acupuncture group was 91 . 4%. And the total efficiency of the western medicine group was 66 . 7%. There were significant differences between two groups ( P < 0 . 05 ) . The treatment efficiency of tinnitus between two groups was also compared . The total efficiency of Chinese medicine combined with electric acupuncture group was 91 . 2%. And the total efficiency of the western medicine group was 78 . 6%. There was no significant difference between two groups . The comparison of dizziness relieving effect between two groups showed that the total efficiency of Chinese medicine combined with electric acupuncture group was 94 . 1%; and the total efficiency of the western medicine group was 73 . 3%. There was no significant difference between two groups . The hemorheological parameters were also improved . In the Chinese medicine combined with electric acupuncture group , indexes such as blood viscosity ratio , plasma viscosity ratio , erythro-cyte electrophoresis time and hematocrit were all improved obviously compared to western medicine group . There was significant difference between two groups ( P < 0 . 05 ) . It was concluded that in the improvement of clinical symptoms of sudden deafness, physical signs and hemorheology, Chinese medicine combined with elec-tric acupuncture receives better effects compared to western medicine .

Activity of tongqiao huoxue decoction on the learning and memory ability of rats with vascular dementia in rats / 中国药学杂志

OBJECTIVE: To study the activity of TQHXD on the learning and memory ability of rats with vascular dementia(VD) and its effects on the content of Ach in cerebral cortex. And to investigate the action mechanism of TQHXD on VD in rats. METHODS: VD model was made by common carotid artery injection of a co-thrombus inducer. The 8-arm radial maze experiment was adopted to evaluate the times of working memory errors and reference memory errors. The changes of the pathological area in hippocampus CA1 were observed by optical microscope. Enzyme-linked immunosorbent assay was used to determine the concentration of Ach in rats cerebral cortex. RESULTS: High and middle dose of TQXHD significantly reduce the times of working memory errors and reference memory errors (P<0.01), definitely improved the anormalies of pathological area in hippocampal CA1, and significantly increased the content of Ach in cerebral cortex (P<0.01). CONCLUSION: TQHXD can significantly ameliorate the learning and memory ability of in VD rats. The mechanism may be related to the improvement of the vertebral body cells anomalies in the hippocampal CA1 region and increasing the content of the Ach in cerebral cortex. Copyright 2012 by the Chinese Pharmaceutical Association.

Effects of Tongqiao Huoxue Decoction on contents of CGRP、 ET、 IL-1?、TNF-? in the brains of rats of cerebral ischemia / 中成药

AIM: To investigate the protective effects and mechanisms of Tongqiao Huoxue Decoction on the rats of cerebral ischemia. METHODS: Cerebral ischemia madel was established on the basis of cerebral thrombus and at the same time ligaturing bilateral carotid arteries.These models were used to observe the protective effects of Tongqiao Huoxue Decoction on contents of CGRP、ET、IL-1?,TNF? in rats′ cerebral ischemica. RESULTS: The results showed that Tongqiao Huoxue Decoction decreased the contents of IL-1?、TNF-?、 ET,and increased the contents of CGRP. CONCLUSION: Tongqiao Huoxue Decoction had effects on anti-cerebral ischemia.The protective effects of Tongqiao Huoxue Decoction are related to decreasing the contents of IL-1?,TNF-?,ET,and increasing the contents of CGRP.