Effect of low-dose aspirin and Danshen injection on hemorheology, vascular endothelial function and oxidative stress in pregnancy-induced hypertension

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1 Journal of Hainan Medical University 2018; 24(6): Journal of Hainan Medical University Effect of low-dose aspirin and Danshen injection on hemorheology, vascular endothelial function and oxidative stress in pregnancy-induced hypertension Hao Li, Ai-Ping Ma Department of Obstetrics and gynecology in Hanchuan People's Hospital of Hubei, Hanchuan, Hubei ARTICLE INFO Article history: Received 2 Mar 2018 Received in revised form 12 Mar 2018 Accepted 15 Mar 2018 Available online 28 Mar 2018 Keywords: Danshen injection Aspirin Pregnancy-induced hypertension Hemorheology Vascular endothelial function Oxidative stress ABSTRACT Objective: To investigate the effect of low dose aspirin and salvia miltiorrhiza injection on hemorrheology, endothelial function and oxidative stress in patients with pregnancy induced hypertension. Methods: One hundred and eighty pregnancy-induced hypertension patients treated in our hospital from April 2015 to November 2016 were selected as study subjects and randomly divided into control group and observation group with 90 cases in each group. The control group was given routine treatment. The observation group was treated with low-dose aspirin plus Salvia miltiorrhiza in the control group. After treatment, blood rheology, vascular endothelial function and oxidative stress were measured in two groups. Results: The levels of MAP and 24 h Upro in both groups were significantly lower than those before treatment. After treatment, the MAP and 24 h Upro levels in the observation group were significantly lower than those in the control group. After treatment, the level of PT was significantly higher than that before treatment, while the level of DD and Fg was significantly lower than that before treatment. Comparing the two groups after treatment showed that the PT level, and the levels of DD and Fg were significantly lower than those in the control group; After treatment, NO levels in both groups were significantly higher than those before treatment, ET-1 and ET-1/NO levels were significantly lower than before treatment, after treatment, ET-1, NO and ET The NO level in the observation group was significantly higher than that in the control group, while ET-1 and ET-1/NO levels were significantly lower than those in the control group; Compared with those before treatment, the levels of SOD in the two groups were significantly increased and MDA significantly decreased after treatment. The SOD and MDA levels in the two groups after treatment showed that the SOD level in the observation group was significantly higher than that in the control group, while MDA level was significantly lower than that of the control group. Conclusion: The combination of low-dose aspirin and Salvia miltiorrhiza injection has significant therapeutic effect on gestational hypertension, and can effectively improve the hemorheological parameters and endothelial function of patients and reduce the oxidative stress injury in patients. It is worth further clinical promotion. 1. Introduction Pregnancy induced hypertension is a common disease of pregnant women in the middle and late pregnancy. Patients showed dizziness, vertigo, nausea and vomiting. In addition to this, there will be Corresponding author: Ai-Ping Ma, Department of Obstetrics and gynecology in Hanchuan People's Hospital of Hubei, Hanchuan, Hubei ma34488@163.com Fund Project: Funding of the Hubei Provincial Health Department Fund Project (Hubei Wei 2016-cbE126). high blood pressure, proteinuria and edema, which has seriously threatened the health of mother and child[1]. The common drug used to treat this disease is Magnesium Sulfate. But it has the disadvantages of aggravating the patient's nausea and vomiting, increasing the feeling of discomfort and so on, and is not good in the curative effect[2]. Studies have shown that the combination of traditional Chinese and Western medicine can be effective in the treatment of pregnancy induced hypertension[3]. The combination of Salvia miltiorrhiza injection and small dose aspirin can effectively prevent and cure pregnancy induced hypertension[4,5], and the

2 64 combined application of these two reports is less. In view of this, we studied the effects of low dose aspirin combined with Danshen Injection on hemorheology, vascular endothelial function and oxidative stress in patients with pregnancy induced hypertension. The report is as follows. 2. Data and methods 2.1. General information A total of 180 cases of pregnancy induced hypertension treated in our hospital from April 2015 to November 2016 were selected as the object of this study. All patients were evaluated in accordance with the diagnostic criteria for pregnancy induced hypertension in the seventh edition of Obstetrics and Gynecology[6], for single pregnancy and successfully completed the treatment. Prepregnancy diabetes, hypertension and abnormal heart and liver function were excluded. The selected patients were randomly divided into the control group and the observation group, with 90 cases in each group. Control group: age 24 to 33 years old, average (27.5±2.3) years; gestational weeks 25 to 38 weeks, average (35.1±2.7) weeks; primipara 60 cases, parturient 30 cases; mean systolic blood pressure (168.5±168.5) mmhg, mean diastolic blood pressure (mmhg).the observation group: age 25 to 34 years old, the average (29±3) years of age; gestational age of 26 to 39 weeks, the average (34.1±3.6) weeks; 58 cases of primipara and multipara 32 cases of illness; 22 cases were mild, 43 moderate cases and 25 severe cases; the average systolic blood pressure (167.9±10.3) mmhg, the average diastolic blood pressure (102.1±6) mmhg. There was no significant difference in age, gestational age and condition between the two groups (P>0.05) Treatment methods All patients were given diazepam sedation, nifedipine, antispasmodic and furosemide Semily Magnesium Sulfate urine routine treatment in our hospital during the period of treatment, the observation group was given small dose of aspirin combined with Danshen injection. The specific method is: Glucose Injection 500 ml 5% mixed with 20 ml salvia injection, intravenous drip, 1 times/ d; another Aspirin Enteric-coated Tablets, morning swallow, 50 mg/ d, two patients were treated for 10 d Monitoring indicators The average arterial pressure (MAP) and the level of 24 h urinary protein (24hUpro) were measured before and after the treatment of 10 d.venous blood was collected from two groups of patients. The prothrombin time (PT), D- two polymer (D-D) and fibrinogen (Fg) were detected before and after treatment with the kit.serum levels of endothelin 1 (ET-1), nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) in two groups were detected by Elisa enzyme activity kit Statistical analysis The data were analyzed by SPSS Paired samples t test was used to compare before and after treatment. The independent sample t test was used to compare the two groups after treatment, indicating the form was mean plus minus standard deviation (Mean ± SD). Two tests were used to analyze the count data, and P<0.05 indicated that the difference was statistically significant. 3. Result 3.1. Changes in the two groups of MAP and 24hUpro According to table 1, after treatment, the levels of MAP and 24 hupro in the two groups were significantly decreased (P<0.05), and the levels of MAP and 24 hupro in the observation group were (104.97±1.61) mmhg and (1.35±0.11) g, respectively, which were significantly lower than those in the control group (115.77±0.47) mmhg and (2.23±0.08) g. The difference was significant (P<0.05). Table 1. MAP and 24 hupro levels in two groups of patients. Group n Time MAP (mmhg) 24hUpro(g) Control group 90 Before treatment ± ±0.07 After treatment ±0.47 * 2.23±0.08 * Observation group 90 Before treatment ± ±0.06 After treatmen ±1.61 * 1.35±0.11 * the observation group was compared with the control group after treatment, 3.2. Changes of hemorheological indexes in two groups of patients before and after treatment As shown in Table 2, there was no significant difference in Fg, PT and D-D levels between the two groups before treatment (P>0.05). After treatment, the level of PT was significantly higher than that before treatment (P<0.05), while the level of D-D and Fg was significantly lower than that before treatment (P<0.05). After comparing the two groups, we found that the level of PT in the observation group was significantly higher than that in the control group (P<0.05), and the levels of D-D and Fg in the observation group were significantly lower than those in the control group (P<0.05). Table 2. The comparison of the changes of Fg, PT and D-D levels in the two groups of patients before and after treatment. Group Time PT (s) D-D (mg/l) Fg (g/l) Control group Before treatment 8.58± ± ±0.12 After treatment 11.45±0.13 * 2.14±0.12 * 3.78±0.23 * Observation Before treatment 8.22± ± ±0.28 group After treatment 14.24±0.19 * 1.15±0.21 * 2.21±0.34 * the observation group was compared with the control group after treatment,

3 Changes of vascular endothelial function in two groups of patients before and after treatment From table 3, there was no significant difference in the levels of ET-1, NO and ET-1/NO between the two groups before treatment (P>0.05). After treatment, the level of NO in the two groups was significantly higher than that before the treatment, while the level of ET-1 and ET-1/NO was significantly lower than that before the treatment (P<0.05). After comparing the levels of ET-1, NO and ET-1/NO in two groups after treatment, the NO level in the observation group was significantly higher than that in the control group (P<0.05), while the level of ET-1 and ET-1/NO in the observation group was significantly lower than that in the control group (P<0.05). Table 3. Changes of vascular endothelial function in two groups of patients before and after treatment. Group Time ET-1 (ng/l) NO (μmol/l) ET-1/NO Control group Before treatment ± ± ±0.23 After treatment ±5.34 * 61.38±1.74 * 2.12±0.11 * Observation Before treatment ± ± ±0.10 group After treatment 94.38±4.27 * 72.89±2.38 * 1.41±0.13 * the observation group was compared with the control group after treatment, 3.4 The level of oxidative stress in the two groups As shown in Table 4, compared with before treatment, the SOD increased significantly in the two groups after treatment (P<0.05), and the MDA was significantly decreased (P<0.05). After analyzing the levels of SOD and MDA in the two groups, we found that the SOD level in the observation group was significantly higher than that in the control group (P<0.05), while the MDA level in the observation group was significantly lower than that in the control group (P<0.05). Table 4. The level of oxidative stress in the two groups. Group n Time MDA (nmol/l) SOD (nu/ml) Control group 90 Before treatment 18.73± ±0.91 After treatment 16.03±0.49 * 92.53±1.11 * Observation group 90 Before treatment 18.67± ±1.55 After treatment 10.67±0.57 * ±1.31 * the observation group was compared with the control group after treatment, 4. Discussion Hypertensive disorder complicating pregnancy occurs more than 20 weeks after pregnancy, which is a common disease in the middle and late pregnancy. The patients often have systemic arteriospasm, narrowing of the lumen, increased peripheral resistance and damage of vascular endothelium. Thus the coagulation factor is induced, which makes the body's coagulation function enhanced and the anticoagulant system weakens. The clinical manifestations of hypertension, proteinuria and edema are present[7]. As for the treatment of hypertensive disorder in pregnancy, it is mainly to depressurization and spasmodic. The antispasmodic drug is the first choice for Magnesium Sulfate, but its effective concentration and poisoning dose are very close. It is easy to cause magnesium poisoning and can inhibit uterine contraction and increase the risk of fetal distress. It is not recommended to use alone in clinical practice[8]. Aspirin is a common drug in the treatment of cardiovascular diseases. It can effectively inhibit the activity of cyclooxygenase, inhibit platelet aggregation, regulate the ratio of prostaglandin to thromboxane, expand blood vessels and lower blood pressure effectively[9,10]. It has been found that aspirin can increase the risk of cardiovascular disease in the treatment of acute myocardial infarction and other cardiovascular diseases, namely aspirin resistance, which severely limits its clinical application[11]. Han Yaling and other studies have found that the increase in the use of other antiplatelet drugs can effectively reduce the incidence of aspirin resistance[12]. Salvia miltiorrhiza injection is a Chinese medicine preparation. Its main active ingredients are tanshinone, Danshensu and so on. It has the function of activating blood and removing blood stasis, resisting platelet aggregation, relaxing smooth muscle, reducing arterial pressure and so on[13]. It can also improve the body arteriospasm, increase the blood supply of the placenta, improve the function of the placenta, and prevent fetal distress[14]. The effects of low dose aspirin combined with Danshen Injection on hemorheology, vascular endothelial function and oxidative stress index in patients with pregnancy induced hypertension were discussed. The results showed that after treatment, the levels of MAP and 24 hupro were significantly decreased in the two groups, and the levels of MAP and 24 hupro in the observation group were significantly lower than those in the control group. It is shown that the combination of Salvia miltiorrhiza injection and small dose aspirin can effectively improve the symptoms of pregnancy induced hypertension, which is in accordance with the results of Zheng Xiaoying[1]. The change of blood rheology is the main characteristic of the patients with pregnancy induced hypertension. The study found that the patient's blood often presents a hypercoagulable state. D-D is a specific degradation product of the body's crosslinked fibrin, and its increase reflects the enhancement of the body's coagulation function and the activation of the fibrinolytic system[15]. Fg is a protein with blood coagulation, which can effectively promote platelet aggregation, increase blood viscosity, and promote thrombosis[16]. PT is an important indicator of clinical

4 66 anticoagulant therapy. The lower the level, the stronger the body's coagulation function[17]. In this study, after treatment, the level of PT was significantly higher than that before treatment (P<0.05), while the level of D-D and Fg was significantly lower than that before treatment (P<0.05). After comparing the two groups, we found that the level of PT in the observation group was significantly higher than that in the control group (P<0.05), and the levels of D-D and Fg in the observation group were significantly lower than those in the control group (P<0.05). The combination of small dose aspirin and Salvia miltiorrhiza injection can effectively improve the hemorheological indexes and reduce the hypercoagulable state of the patients with pregnancy induced hypertension. In addition, the changes in vascular endothelial function are also the frequent changes in patients with pregnancy induced hypertension. NO is a new information transfer molecule produced by endothelial cells. It is also an important relaxation factor. It plays an important role in maintaining endothelial function and regulating blood pressure[18]. ET-1 is a potent vasoconstrictor and is a sensitive indicator of the condition of hypertensive patients[19]. The study found that after treatment, the level of NO in the two groups was significantly higher than that before the treatment, while the level of ET-1 and ET-1/NO was significantly lower than that before the treatment (P<0.05). After comparing the levels of ET-1, NO and ET-1/NO in two groups after treatment, the NO level in the observation group was significantly higher than that in the control group (P<0.05), while the level of ET-1 and ET-1/NO in the observation group was significantly lower than that in the control group (P<0.05). It shows that the combination of small dose aspirin and Salvia miltiorrhiza injection is effective in improving the vascular endothelial function of patients with pregnancy induced hypertension. Studies have shown that changes in oxidative stress play an important role in the pathogenesis of pregnancy induced hypertension[20]. During pregnancy, the women had faster metabolism, the placenta needed sufficient oxygen supply, the oxygen consumption increased significantly, and the formation of free radicals increased. In order to eliminate peroxidation products in the body, the body can prevent peroxidation damage by increasing the mechanism of peroxidase in the body. SOD is an antioxidant enzyme in the body, which can effectively remove oxygen free radicals produced during the activities of body metabolism and prevent oxidative damage[21]. MDA is one of the final products of lipid peroxidation. The level of the body is directly responsive to the extent of the body's damage[22]. This study showed that small dose of aspirin combined with Salvia miltiorrhiza injection could effectively increase the level of SOD and NO in the patient's body, reduce the content of MDA and reduce the damage of oxidative stress. Dong Xiying[2] and other studies also found that Salvia miltiorrhiza injection combined with low-dose aspirin can effectively reduce the oxidative stress level in hypertensive disorder complicating pregnancy, which is similar to the results of this study. It is indicated that low dose aspirin combined with Danshen injection can effectively remove oxygen free radicals and promote antioxidant enzyme activity, thereby reducing oxidative stress on the body. In conclusion, low dose aspirin combined with Salvia miltiorrhiza injection can produce effective treatment for hypertensive disorder complicating pregnancy, improve hemorheological indexes, enhance endothelial function and reduce oxidative stress level. It is worthy of clinical application. 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