ABSTRACT
ObjectiveTo establish a mouse model of basilar artery dolichoectasia （BAD） and explore the mechanism of modified Tongqiao Huoxuetang （JTQHX） in regulating BAD via phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSixty C57/BL6 female mice were randomized into sham operation （injected with 10 U·mL-1 inactivate elastase）， model， atorvastatin calcium tablets （2.6 mg·kg·d-1）， and low- and high-dose （crude drug 3.4， 17 g·kg-1·d-1， respectively） JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL-1 elastase. After 14 days of modeling， the sham operation group and model group were administrated with equal volumes of pure water by gavage， and other groups with corresponding drugs for 2 months. The levels of interleukin-6 （IL-6） and calpain （LpA） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Verhoeff 's Van Gieson （EVG） staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL） was employed to examine the apoptosis rate of vascular smooth muscle cells （VSMCs）. Image Pro Plus was used to observe and calculate the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group， the model group showed lowered IL-6 level （P<0.01）， no significant change in LpA level， increased apoptosis of VSMCs （P<0.01）， and increased curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.01）. Furthermore， the modeling up-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01） and aggravated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group， 2 months of treatment with JTQHX elevated the IL-6 level （P<0.01）， reduced the apoptosis of VSMCs （P<0.01）， decreased the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.05， P<0.01）， and down-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01）. In addition， the treatment alleviated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation， expansion， and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.
ABSTRACT
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><sup>2</sup>=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.
ABSTRACT
Objective::To explore the clinical efficacy of Tongqiao Huoxuetang plus acupuncture on post-stroke cognitive impairment (PSCI) and its effect on neurotransmitters and neurological function of patients. Method::Totally 122 PSCI patients admitted in our hospital from January 2017 to March 2019 were randomly divided into observation group and control group by simple random number table method, with 61 patients in each group. Both groups were given oral donepezil hydrochloride tablets. The control group was given acupuncture treatment, while the observation group was given Tongqiao Huoxuetang plus acupuncture in addition to therapy of control group. All patients were treated continuously for 4 weeks. The clinical efficacy was compared between two groups. Before and after treatment, the general cognitive function of two groups was tested by mini-mental state examination (MMSE), changes of their neurologic impairment and daily living ability were evaluated by National institutes of health stroke scale (NIHSS) and Barthel index (BI) respectively, and euzymelinked immunosorbent assay was adopted to test the levels of neurotransmitters [acetyl choline (ACh), dopamine (DA), noradrenaline (NE), 5-hydroxytryptamine (5-HT)] and neurologic impairment markers [neuronspecific enolase (NSE), visinin-like protein-1 (VILIP-1), myelin basic protein (MBP)]. And the occurrence of adverse reactions was recorded. Result::The overall effective rate of the observation group was 91.8% (56/61), which was much higher than 78.7% (48/61) of control group (P<0.05). After treatment, both groups saw much higher MMSE and BI scores but lower NIHHS scores than before treatment (P<0.05), and above indicators in observation group were improved more significantly than those in control group over the same period after treatment (P<0.05). The levels of serum ACh, DA, NE and 5-HT after treatment were obviously higher than those before treatment (P<0.05), and observation group had significantly higher ACh, DA, NE and 5-HT levels than control group over the same period (P<0.05). After treatment, both groups witnessed a great decrease in NSE, VILIP-1, MBP (P<0.05), while the observation group saw dramatically lower NSE, VILIP-1, MBP levels than control group over the same period after treatment (P<0.05). Neither of two groups saw serious adverse reactions. Conclusion::In treating PSCI, Tongqiao Huoxuetang plus acupuncture can significantly improve neurological function of the patients, which may be due to increase of neurotransmitters. Besides, Tongqiao Huoxuetang plus acupuncture is proved to be generally effective in promoting the recovery of patients' neurological function and enhancing their abilities in daily life, with a good tolerance among patients.
ABSTRACT
Objective:To investigate the protective effect of cerebrospinal fluid containing Tongqiao Huoxuetang (TQHXT) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (BMECs), in order to explore the underlying mechanisms. Method:Primary BMECs were extracted by enzymatic digestion, and the cells were randomly divided into six groups: the normal control group, the OGD/R group, the TQHXT group（20%）, the nimodipine（NMDP） group (10 μmol·L-1), the cabozanix group (1 μmol·L-1) and the combination group. Except for the normal control group, the cells in the other groups were rapidly reoxygenated for 24 h after 2 h of oxygen-glucose deprivation, the OGD/R modeling was performed, and the rats were administered with drugs by groups. BMECs were identified by cell immunofluorescence staining, morphological and ultrastructural changes of OGD/R-induced BMECs were observed, and changes in cell transmembrane resistance (TEER) were detected. The levels of nitric oxide (NO), the activity of lactate dehydrogenase (LDH), the fluorescence intensity of reactive oxygen species (ROS) and the content of tissue-type plasminogen activator (tPA) were measured with kits. Intracellular Ca2+ concentration and cell apoptosis were detected by flow cytometry, and the expression of CD34 was observed. The protein expressions of zonula occluden-1 (ZO-1), vascular endothelial growth factor (VEGF), adhesion kinase (FAK), and Paxillin were detected by Western blot. Result:Compared with the normal control group, the cells in the OGD/R group were shrinking and rounded, TEER value and ZO-1 protein expression in cells were significantly decreased, the contents of NO, LDH and ROS in cells were significantly increased, the content of tPA was significantly decreased, the concentration of Ca2+ and the apoptosis in the cells were significantly increased, CD34 was expressed in cells, and the protein expressions of VEGF, FAK and Paxillin were significantly increased (P<0.01). Compared with the OGD/R group, cell damage in the TQHXT group was significantly improved, the TEER value and ZO-1 protein expression in cells were significantly increased, the contents of NO, LDH and ROS in cells were significantly reduced, the content of tPA was significantly increased, the concentration of Ca2+ and the apoptosis in the cells were significantly reduced, CD34 expression increased in cells, and the protein expressions of VEGF, FAK and Paxillin were significantly increased (P<0.05，P<0.01). Conclusion:CSF containing TQHXT protects BMECs from OGD/R injury possibly by promoting angiogenesis through the VEGF-VEGFR2/FAK/Paxillin signaling pathway.
ABSTRACT
Objective:To observe the effect of modified Tongqiao Huoxuetang on circulating blood flow and wall shear stress of vertebrobasilar dolichoectasia (VBD) due to blood stasis and channel blockage. Method:A total of 97 patients admitted in our department from October 2017 to August 2019 were collected. The traditional Chinese medicine (TCM) syndromes were consistent with blood stasis and channel blockage, and diagnosed as VBD by magnetic resonance angiography (MRA). The patients were divided into experimental group (48 cases) and control group (49 cases). Control group was given basic therapy and placebo of TCM, while treatment group was given basic therapy and modified Tongqiao Huoxuetang for 30 days. The degree of relief of vertigo symptoms, vertigo symptom scale (VSS), activity balance confidence (ABC), transcranial doppler (TCD) bilateral vertebral artery and basilar artery blood flow velocity [systolic blood flow velocity (Vs), mean blood flow velocity (Vm), diastolic blood flow velocity (Vd)], mean blood flow differences between (MFV), pulsatility index, resistance index (RI), and wall shear force (WSS) were observed before and after treatment. Result:Compared with control group before treatment, the score of ABC scale in control group after treatment was markedly higher, while the score of VSS was significantly lower (P<0.05). However, there was no statistical significance in the score of vertigo symptom. Compared with treatment group before treatment, the symptom grade of vertigo degree and the score of VSS in treatment group after treatment were substantially lower, while the score of ABC scale was significantly higher (P<0.05). Compared with control group, the score of vertigo degree symptoms and VSS in treatment group were markedly lower, while the score of ABC scale was significantly higher (P<0.05). Compared with control group before treatment, Vm, MFV and WSS of bilateral vertebral artery in control group after treatment were substantially higher, while RI was significantly lower (P<0.05). However, there were no statistical significances in Vs, Vd and PI in control group before and after treatment. Compared with treatment group, Vs, Vd, Vm, MFV and WSS of bilateral vertebral artery in treatment group after treatment were markedly higher, while RI was significantly lower (P<0.05). However, there was no statistical significance in PI of experimental group before and after treatment. Compared with control group after treatment, Vs, Vd, Vm, MFV and WSS of bilateral vertebral artery in treatment group after treatment were substantially higher, while there was no statistical significance in PI and RI. Before and after treatment, there were similar changes in blood flow parameters of the basilar artery and bilateral vertebral artery. Conclusion:Modified Tongqiao Huoxuetang could improve the clinical symptoms of dizziness or vertigo in patients of VBD due to blood stasis and channel blockage, and the mechanism might be related to the improvement of post-circulation hemodynamics by Tongqiao Huoxuetang.
ABSTRACT
Objective::To observe the effect of modified Tongqiao Huoxuetang combined with stent thrombectomy in treating acute cerebrovascular occlusion. Method::A total of 120 cases were randomly divided into control group and observation group, with 60 cases in each group. The control group received stent thrombectomy, while the observation group received modified Tongqiao Huoxuetang combined with stent thrombectomy. The clinical symptoms [health neural function defect scale stroke scale scores(NIHSS), activities of daily living(ADL), mini mental state examination(MMSE)], hemodynamic indexes [high-shear reduction viscosity(HSRV), medium-shear reduction viscosity(MSRV), low-shear reduction viscosity(LSRV), whole blood plasma viscosity(WBV)], vascular endothelial functions [serum nitric oxide synthase(NOS), endothelin-1(ET-1), vascular endothelial growth factor(VEGF)] were observed. The clinical efficacy and the incidence of adverse reactions were compared between two groups. The blood routine, urine routine, heart, liver and kidney function, incidence of cerebral hemorrhage in two groups were observed during the treatment. Result::There were 4 cases were shed in control group and 2 cases in observation group during the study period. The total effective rate in observation group was 94.8%(55/58), which was higher than 83.9% of the control group(47/56)(P<0.05). The NIHSS in observation group was lower than that in control group(P<0.05), whereas ADL and MMSE were higher than those in control group(P<0.05). The hemorheological indexes in observation group were lower than those in control group(P<0.05), NOS and VEGF in observation group were higher than those in control group(P<0.05), and ET-1 score was lower than that in control group(P<0.05). During the study period, the incidence of cerebral hemorrhage was 7.14%(4/56) in control group and 8.6%(5/58) in observation group, with no significant difference. Conclusion::Modified Tongqiao Huoxuetang combined with stent thrombectomy could significantly improve the clinical symptoms, hemorheology and vascular endothelial function of patients with acute cerebrovascular occlusion, and so is worthy of clinical promotion and application.
ABSTRACT
Objective: To discuss the clinical efficacy of modified Tongqiao Huoxuetang combined with ‘Huiyang Jiuzhen’ in treating post-stroke cognitive impairment (PSCI) and its mechanisms in resisting inflammation and oxidant stress and ameliorating hemorheology. Method: One hundred and twenty-two patients were randomly divided into control group (61 cases) and observation group (61 cases) by random number table. Both groups got Donepezil tablets, 10 mg/time, 1 time/day, and Nicergoline tablets, 20 mg/time, 3 times/days. Patients in control group got ‘Huiyang Jiuzhen’, 1 time/day, 6 times/week. In addition to the therapy in control group, patients in observation group got modified Tongqiao Huoxuetang, 1 dose/day. And a course of treatment was 8 weeks. Before treatment and at the 4th week and 8th week after treatment, scores of mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were discussed. And activity of daily living scale (ADL), syndrome of blood stasis and cerebral collaterals were graded. And levels of Interleukin-6 (IL-6) before and after treatment, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), oxidized low density lipoprotein (Ox-LDL), superoxide dismutase (SOD), malondialdehyde (MDA), hemorheology were detected. Result: According to the rank sum test, the clinical efficacy in observation group was better than that in control group (Z=1.976, Pth week and 8th week after treatment, score of MMSE and MoCA were higher than that in control group (PPPα, CRP, DA and Ox-LDL were lower than those in control group (PPPConclusion: In addition to the routine therapy of western medicine, modified Tongqiao Huoxuetang combined with ‘Huiyangjiuzhen’ can improve patients cognitive function and daily life ability, have effects in resisting inflammation and oxidation and ameliorating hemorheology, and can promote the recovery of cognitive function.
ABSTRACT
Objective:This study aims to observe the clinical efficacy of Tongqiao Huoxuetang in treating blood stasis resistance type vascular cognitive impairment, and explore its mechanism of action. Method:A total of 60 patients who met the inclusion standards and were diagnosed as blood stasis resistance type vascular cognitive impairment were randomly divided into treatment group and control group, 30 patients in each group. Donepezil hydrochloride was administered orally in control group based on internal medicine treatment at an initial dose of 5 mg/day, changed to 10 mg/day 4 weeks later. Patients in treatment group additionally received Tongqiao Huoxuetang based on donepezil hydrochloride. Both groups were treated for 3 months. Changes of symptoms were assessed by syndrome scores; cognitive function was assessed by the mini-mental scale (MMSE); daily living ability was assessed by the activity of daily living scale (ADL), and changes of local blood perfusion (CBF value) was assessed by brain magnetic resonance perfusion imaging arterial spin labeling (MRI-ASL). Changes of homocysteine levels in plasma were measured by using an automated biochemical analyzer. Result:① The values of traditional Chinese medicine(TCM) syndrome scores (SDSVD) were significantly improved in both groups after treatment, and the improvement was more obvious than that of control group (PPPPP P Conclusion:The combination of Tongqiao Huoxuetang combined with donepezil hydrochloride can effectively improve the cognitive ability and daily living ability of the patients with vascular dementia, improve the cerebral blood flow perfusion and decrease the level of homocysteine, so it is worth popularizing in clinical practice.