Clinical characteristics of Danshen Ligustrazine injection in the treatment of coronary heart disease with hypertension-A real world study

Objective:To explore the characteristics and rules of Danshen Ligustrazine Injection in the treatment of coronary heart disease with hypertension.Methods:From the information systems of 12 tertiary tier-one hospitals across the country,we extracted the medical data of the application of Danshen Ligustrazine Injection in the treatment of patients with coronary heart disease and hypertension.After normalization,the model was established by Apriori algorithm,and the association rules were analyzed by Clementine 12.0 software.Results:Most of the 1928 patients were between 75 and 90 years old(54.26%).There were more males than females,most with type 2 diabetes,cerebral infarction,etc.Each dose was more than 10 mL(52.78%).Aspirin enteric-coated tablets(67.63%),L-carnitine injection(58.77%),and atorvastatin calcium capsules(50.93%)were often used in combination with safflower yellow pigment(22.20%),Shexiang Baoxin Pill(16.55%),Suxiao Jiuxin Pill(15.09%);the most commonly used combination of western medicine was anticoagulant thrombolytic and antiplatelet drugs(85.84%),and the type of Chinese medicine was Huoxuehuayu(72.98%);The most common combination of two western medicines was L-carnitine injection+aspirin enteric-coated tablets,with a support of 41.9%;The most common combination of two Chinese and western medicines is western medicine·anti-anginal medicine+western medicine·anticoagulant thrombolytic and antiplatelet drugs with a support of 67.6%.Conclusion:Danshen Ligustrazine injection is mainly used in elderly patients with coronary heart disease and hypertension,with many comorbidities.The dosage standard needs to be optimized.The combination of drugs and guidelines should coordinate with each other,which provide clues for clinical diagnosis and treatment and optimization of medication.

Effect of Ligustrazine Injection on Levels of Interleukin-4 and Interferon-γin Patients with Bronchial Asthma

Objective： To explore the effect of ligustrazine injection （LI） on serum levels of interleukin-4 （IL-4） and interferon- -γ （IFN- -γ ） in patients with bronchial asthma and determine the mechanism of action of LI in preventing and treating asthma. Methods： Sixty-eight patients with mild or moderate bronchial asthma were assigned to two groups equally according to their sequence number, odd or even. The conventional treatment was administered to both groups, and LI was given to the treatment group by ultrasonic spray inhalation twice a day but not to the control group. The therapeutic course for all was 2 weeks. Further, 30 healthy subjects who had no history of smoking were enrolled as the normal control group. The clinical condition scores, frequency of attacks and dosage of Terbutaline inhaled were scored and recorded on the first day of hospitalization （before treatment） and after treatment. At the same time, the indexes of lung function, including forced expiratory volume in one second （FEV1）, forced expiratory volume in one second to forced vital capacity ratio （FEV1%） and the peak expiratory flow （PEF） were determined before treatment. The levels of IL-4 and IFN--γ in peripheral blood were detected by ELISA before and after treatment, and compared with that of the healthy control group. Results： After treatment, the clinical condition scores were found to be lower, indexes of lung function were elevated, but serum level of IL-4 and ratio of IL-4/IFN-γwere reduced in both groups, showing significant differences as compared to those before treatment （P〈0.05）. However, the changes in all the indexes were more significant in the treatment group than in the control group, also showing statistical significance （P〈0.05）. No significant difference was revealed when IFN--γ levels were compared before and after treatment in both groups, though a lowering trend could be seen, significant difference could not be found in the comparison of IFN--γ levels between groups after treatment （P〉0.05）. Conclusion： LI shows good clinical effect in treating bronchial asthma, and its mechanism might be related to the suppression of the synthesis of IL-4, thus leading to the inhibition of TH2 cell subset preponderant response and immune equilibrium regulation.

Anti-fibrotic Effects of Salvia miltiorrhiza and Ligustrazine Injection on LX-2 Cells Involved with Increased N-myc Downstream-Regulated Gene 2 Expression

Objective: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection（SML） on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2（NDRG2, a tumor suppressor gene）. Methods: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×10;cells/mL and cultured for 24 h followed by the application of different concentrations of SML（1, 2, 4 and 8 μL/mL）. Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and β-catenin were measured by Western blot. Results: With the exception of the 1 and 2 μL/mL concentrations, 4 and 8 μL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h（P<0.05）. With the exception of the 1 and 2 μL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of β-catenin was unaffected. Conclusion: SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.

Effect of Ligustrazine Injection on Vascular Endothelial Cell of The Patients with Arteriosclerosis Obliterans

Objective: To study the effect of ligustrazine injection (LI) on vascular endothelial cell of the patients with arteriosclerosis obliterans (ASO) and explore the new pathway of investigating effective vascular protective agents in Chinese medicinal herbs. Methods: Forty-six patients with ASO in the LI group treated by LI were observed, their circulating endothelial cells (CEC) were detected quantitatively before and after treatment. The results were compared with the CEC of 53 cases of healthy persons (control group) in the same period. Results: In the LI group, the immediate cure rate was 45.7% (21 cases), markedly effective rate 36.9% (17 cases) and the effective rate 17.4% (8 cases). The CEC of patients before treatment was 4.39±1.76/0.9μl, which was significantly higher than that of the healthy persons (1.53±0.42/0.9μl). It could be reduced after treatment, along with the improvement of symptoms and signs, to 2.43±0.87/0.9μl, P＜0.01. Conclusion: LI in treating ASO not only displays extraordinary effect, but also has good effect in curing the damage of endothelial cells.

Effect of salviae miltiorrhizae and ligustrazine hydrochloride injection on axonal regeneration and nerve growth factor expression in a rat model of sciatic nerve injury

BACKGROUND： Studies have shown that both salviae miltiorrhizae and ligustrazine can promote protein expression of nerve growth factor （NGF） and regeneration of peripheral nerve. OBJECTIVE： To verify the effect of salviae miltiorrhizae and ligustrazine hydrochloride injection on axonal regeneration and NGF protein expression in a rat model of sciatic nerve injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Traditional Chinese Medicine and the Institute of Bioengineering of Jinan University from July to December 2008. MATERIALS： Salviae miltiorrhizae and ligustrazine hydrochloride injection （containing 20 mg salviae miJtiorrhizae and 100 mg ligustrazine per 100 mL injection） was provided by Guizhou Baite Pharmaceutical, China; salviae miltiorrhizae and ligustrazine decoctions （containing 1 g raw drug per 1 mL decoction） were provided by Guangzhou Baiyunshan Factory for Traditional Chinese Medicine, China; rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Biosynthesis Biotechnology, China. METHODS： A total of 80 healthy, male, Sprague Dawley rats were used to establish a sciatic nerve injury model via neurotomy, and were then randomly assigned to 4 groups： salviae miltiorrhizae and ligustrazine hydrochloride injection group （intraperitoneal injection of 35 mL/kg per day salviae miltiorrhizae and ligustrazine hydrochloride injection）, saIviae miltiorrhizae group （intragastric peffusion of 2 mL salviae miltiorrhizae）, ligustrazine group （intragastric peffusion of 2 mL ligustrazine）, and model group （intraperitoneal injection of 35 mL/kg per day saline）, with 20 rats in each group. Thereafter, rats in each group were then divided into 4 subgroups according to varying time points of 1, 2, 4, and 8 weeks post-surgery, with 5 rats in each subgroup. MAIN OUTCOME MEASURES： Axons were quantified using chromotrope 2R-brilliant green and silver staining combined with image analysis to calculate the axonal regeneration rate; NGF expression was detected using immunohistochemistry and Western blot analysis; toe interspace was measured by behavior at 4 and 8 weeks. RESULTS： With increasing time after sciatic nerve expression, and toe interspace gradually increased njury, the axonal regeneration rate, NGF protein At 4 and 8 weeks post-surgery, axonal regeneration rate and NGF protein expression were significantly increased in the injured tissue of the salviae miltiorrhizae and ligustrazine hydrochloride injection, salviae miltiorrhizae, and ligustrazine groups, compared with the model group （P 〈 0.05 or P 〈 0.01）, and toe interspace was remarkably enlarged （P 〈 0.05 or P 〈 0.01）, especially in the salviae miltiorrhizae and ligustrazine hydrochloride injection group. CONCLUSION： Salviae miltiorrhizae and ligustrazine hydrochloride injection promoted axonal regeneration and NGF protein expression in the injured sciatic nerve, and also enhanced neurofunctional recovery. Its effect was superior to salviae miltiorrhizae or ligustrazine alone.