沙库巴曲缬沙坦钠联合环磷腺苷葡胺治疗舒张性心力衰竭的临床研究

目的 对黄芩茎叶水浸液进行系统的安全性评价，以期为黄芩药材的综合利用提供安全性依据。方法 称取黄芩茎叶，经2次90℃的水浸泡30 min，将2次滤液合并蒸发浓缩至所需浓度作为受试物。急性毒性实验：设置对照组和受试物（15 g/kg）组，一次性给药，观察并记录给药后14 d内的毒性反应、死亡情况和体质量变化。遗传毒性实验：分别进行了Ames试验、小鼠骨髓微核试验和小鼠精子畸形试验。长期毒性实验：设置受试物低、中、高剂量（0.417、4.167、8.333 g/kg）组和对照组，给药90 d，检测指标包括动物体质量、摄食量、血液学指标、血清生化、脏器质量及系数和病理组织学检查。致畸试验：将雌、雄大鼠1：1放置使其受孕，设置受试物低、中、高剂量（0.417、4.167、8.333 g/kg）组、对照组和阳性对照（维生素A醋酸酯，1 g/kg）组，在受孕的第7~16天，每天ig给药，于第20天断头处死，记录子宫质量，吸收胎、早死胎、晚死胎及活胎数，逐一记录胎仔性别、体质量、体长、检查胎鼠外观有无异常，并进行骨骼检查。结果 小鼠急性毒性最大耐受量（MTD）为15 g/kg，按急性毒性分级，属无毒级。3项遗传毒性试验结果均为阴性，未见受试物有致突变作用。90 d喂养试验未见动物中毒性损伤改变。致畸试验表明，未见母体毒性，无致畸作用。结论 黄芩茎叶水浸液对受试动物无明显毒性。

Clinical study on sacubitril valsartan sodium combined with meglumine adenosine cyclophosphate in treatment of diastolic heart failure

Objective To explore the clinical efficacy of sacubitril valsartan sodium combined with meglumine adenosine cyclophosphate in treatment of diastolic heart failure. Methods Patients (136 cases) with diastolic heart failure in Tianjin Chest Hospital from March 2017 to March 2019 were randomly divided into control (68 cases) and treatment (68 cases) groups. Patients in the control group were iv administered with Meglumine Adenosine Cyclophosphate Injection, 90 mg added into 5% Glucose Injection 500 mL, once daily. Patients in the treatment group were po administered with Sacubitril Valsartan Sodium Tablets on the basis of the control group, and the initial dosage was 50 mg/time, twice daily, then gradually increase to 400 mg/d. Patients in two groups were treated for 15 d. After treatment, the clinical efficacy was evaluated, and the cardiac function indexes of LVEF, LVESD, LVEDD, and LVESV, 6 min walking distance, MLHFQ score, and the serum levels of BNP, IL-6, hs-CRP and ALD in two groups before and after treatment were compared. Results After treatment, the clinical efficacy and in the control and treatment groups was 73.53% and 95.59%, respectively, and there were differences between two groups (P<0.05). After treatment, the LVEF in two groups was significantly increased (P<0.05), but the LVESD, LVEDD and LVESV levels in two groups were significantly decreased (P<0.05), and the cardiac function indexes in the treatment group were significantly better than those in the control group (P<0.05). After treatment, 6 min walking distance in two groups was significantly increased (P<0.05), but MLHFQ score in two groups were significantly decreased (P<0.05), and the indexes in the treatment group were significantly better than those in the control group (P<0.05). After treatment, the serum levels of BNP, IL-6, hs-CRP and ALD in two groups were significantly decreased (P<0.05), and which in the treatment group were significantly lower than those in the control group (P<0.05). Conclusion Sacubitril valsartan sodium combined with meglumine adenosine cyclophosphate in treatment of diastolic heart failure can improve the heart function of patients, improve exercise tolerance, which has a certain clinical application value.