ETM Experimental and Therapeutic Medicine 1792-0981 1792-1015 D.A. Spandidos 10.3892/etm.2018.6173 ETM-0-0-6173 Articles Effects of compound Danshen injection combined with magnesium sulfate on serum MPO and hs-CRP in patients with severe preeclampsia YangKun 1 DongGaoxia 1 TianYing 2 LiJian 3 Department of Obstetrics, The Second People's Hospital of Liaocheng, Liaocheng, Shandong 252600, P.R. China Department of Obstetrics, Zhangqiu Maternity and Child Care Hospital, Jinan, Shandong 250200, P.R. China Department of Obstetrics, Qingdao Central Hospital, Qingdao, Shandong 266042, P.R. China Correspondence to: Dr Jian Li, Department of Obstetrics, Qingdao Central Hospital, 127 Siliu Nan Road, Qingdao, Shandong 266042, P.R. China, E-mail: drlijian17@163.com 07 2018 17 05 2018 16 1 167 170 07032018 11052018 Copyright: © Yang et al. 2018 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Effects of compound Danshen injection combined with magnesium sulfate on serum myeloperoxidase (MPO) and hypersensitive C-reactive protein (hs-CRP) in patients with severe preeclampsia (PE) were investigated. Five hundred patients with severe PE were randomly divided into early-onset observation, early-onset control, late-onset observation and late-onset control groups. Control group was treated with magnesium sulfate, while patients in observation group were treated with magnesium sulfate combined with compound Danshen injection. Serum levels of MPO and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA) and turbidimetric assay. The effects of compound Danshen injection combined with magnesium sulfate on the above indexes were observed. Serum levels of MPO and hs-CRP significantly decreased in early-onset observation, late-onset observation, early-onset control and late-onset control groups after treatment (p<0.05). After treatment, levels of MPO and hs-CRP were significantly lower in early-onset observation group than in early-onset control group (p<0.05), and levels of MPO and hs-CRP were also significantly lower in late-onset observation group than in late-onset control group (p<0.05). Total effective rate of early-onset observation group and late-onset observation group were higher than that of early-onset control group and late-onset control group. Compound Danshen injection combined with magnesium sulfate achieved better treatment outcomes in the treatment of severe PE than magnesium sulfate alone. The combined treatment can effectively reduce the serum levels of MPO and hs-CRP.

 MPO severe preeclampsia hs-CRP compound Danshen injection magnesium sulfate Introduction

As a pregnancy-specific disease, preeclampsia (PE) seriously affects the health of pregnant women and the fetus. Severe PE may even bring damage to organs (1,2). At present, the pathogenesis of PE is still unclear, and most scholars believe that PE is caused by systemic vascular endothelial injury after placental pathophysiological changes (3,4). The pathogenesis of PE is also very complex, and may be associated with placental ischemia, genetic predisposition, immune adaptation and oxidative stress response (5,6). Hypersensitive C-reactive protein (hs-CRP) is an acute inflammatory protein that is synthesized by hepatocytes. As a hemoglobinase, myeloperoxidase (MPO) is a specific marker of myeloid cells. Rosa et al (7,8) found that MPO level was increased in patients with diabetes, hypertension and other metabolic diseases, suggesting that MPO is involved in the development of PE. Previous studies also showed that hs-CRP was an independent risk factor for cardiovascular disease (9). With Salvia, Panax, and borneol as major ingredients, compound Danshen injection has been widely used in the treatment of heart diseases such as angina (10). With the protective effects on blood vessel dilation, nerve and glia, magnesium sulfate can be used in the standard treatment of PE (11). In this study, serum levels of hs-CRP and MPO in 500 patients with severe PE were detected, and the effects of compound Danshen injection combined with magnesium sulfate on levels of serum MPO and hs-CRP in patients with severe PE were investigated.

 Patients and methods <sec> <title>Selection of patients

A total of 500 patients with severe PE were selected in The Second People's Hospital of Liaocheng (Liaocheng, China) from October 2015 to May 2017. The patients included 250 with early-onset severe PE and 250 patients with late-onset severe PE. The 250 cases of early-onset PE were randomly divided into 125 cases of early-onset observation group and 125 cases of early-onset control group. Similarly, 250 cases of late-onset PE were also randomly divided into 125 cases of late-onset observation group and 125 cases of late-onset control group. The patients met the diagnostic criteria of PE described in ‘Obstetrics and Gynecology’. Inclusion criteria: Blood pressure continually increased after the 20th week of pregnancy: Systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg; serum creatinine ≥1.2 mg/dl; platelet <100,000/ml (<100×109/l); proteinuria ≥2.0 g/24 h, or proteinuria using random urine samples (++). The onset gestational weeks <34 weeks was treated as early onset, and the onset gestational weeks ≥34 weeks was treated as late onset. Exclusion criteria: Patients with diabetes, kidney, infectious and blood system diseases; patients without complete clinical data; patients with a recent medication history; patients with a history of smoking and drinking and other health damaging habits; patients gave up treatment. The patients signed informed consent, and this study was approved by the Ethics Committee of The Second People's Hospital of Liaocheng.

 Treatment

Patients in early-onset and late-onset control group were subjected to intravenous injection (30 min) of 5 g magnesium sulfate (SFDA approval no. 201208; Tianjin Kingyork Group Co., Ltd., Tianjin, China) in 20 ml 5% glucose, then the patients were treated with intravenous injection (30 min) of 15 g magnesium sulfate in 500 ml 5% glucose with a speed of 1–2 g/h, and 25–30 g magnesium sulfate was used every day for 10 days. Besides treatment with magnesium sulfate, patients in early-onset and late-onset observation group were also intravenously injected with compound Danshen injection (production batch no. 140514, 10–20 ml in 250 ml 5% glucose; Tasly Pharmaceuticals, Inc., Tianjin, China), once per day for 10 days. Sedative and intracranial pressure drugs were also used to assist the treatment.

 Detection methods and evaluation

Serum levels of hs-CRP and MPO before and 10 days after treatment were detected. Fasting venous blood samples were collected to prepare serum samples. Serum samples were stored in a fridge (−4°C) before use. Serum levels of hs-CRP were measured by the turbidimetric method, using BN Prospec automatic protein analyzer (Siemens AG, Munich, Germany). Serum levels of MPO was determined by enzyme-linked immunosorbent assay (ELISA) using the kit provided by R&D Systems, Inc. (Minneapolis, MN, USA). Efficacy evaluation criteria: Cure: Patients with proteinuria, blood pressure and other signs all returned to normal. Improved: Patients with improved proteinuria, blood pressure and other signs, and the symptoms are relieved. Invalid: No change in symptoms.

 Statistical analysis

The data were processed using SPSS 22.0 statistical software (IBM Corp., Armonk, NY, USA). Data were first subjected to normal distribution test. Measurement data with normal distribution were expressed by, and t-test was used for comparison between two groups. Comparison of levels before and after treatment were performed by paired t-test. Measurement data with non-normal distribution were expressed by the median values, and comparisons between groups was performed by Wilcoxon test. ANOVA was used for comparison among multiple groups and the post hoc test was Least Significant Difference test. Ratios were compared by χ2 test. P<0.05 was considered to indicate a statistically significant difference.

 Results <sec> <title>Comparison of general information

Significant higher gestational age and white blood cell count were found in late-onset group than in early-onset group (p<0.05). No significant differences in age, pre-pregnancy BMI, pregnancy BMI and blood pressure were found between late-onset group and early-onset group (p>0.05) (Table I).

 Comparison of serum levels of MPO and hs-CRP before and after treatment

After treatment, significantly lower levels of MPO and hs-CRP were found in early-onset observation group than in early-onset control group (p<0.05). Similarly, significantly lower levels of MPO and hs-CRP were found in late-onset observation group than in late-onset control group (p<0.05) (Table II).

 Comparison of clinical efficacy

Total effective rate was significantly higher in early-onset observation group and late-onset observation group than in early-onset control group and late-onset control group (p<0.05) (Table III).

 Discussion

PE is a pregnancy-specific disease, and the incidence rate is ~5% (12). PE can increase the risk of hypertension and other cardiovascular and cerebrovascular diseases, and the recurrence rate is high (13,14). Magnesium sulfate is widely used in the treatment of PE. Magnesium sulfate can reduce intracranial pressure and bring sedation effects. Magnesium sulfate can also produce non-competitive antagonism to reduce Ca2+ concentration (15). Compound Danshen injection can improve the metabolic dysfunction caused by cell ischemia (16). Mizutani et al showed that the combination of magnesium sulfate and compound Danshen injection can effectively improve renal function and blood coagulation in patients with PE (17). In this study, effects of compound Danshen injection combined with magnesium sulfate on serum levels of MPO and hs-CRP in patients with severe PE were explored.

In this study, strict inclusion and exclusion criteria were used to select patients. So, the credibility of the results of the study was ensured. In addition, based on our knowledge, expression of MPO in severe PE has not been previously reported.

hs-CRP is a sensitive indicator of inflammation in the body's inflammatory response, and the mechanism of its function is closely related to inflammatory injury and vascular endothelial dysfunction (18). After vascular endothelial damage, the substances used to relax blood vessels will be reduced, so blood pressure will be increased (19). Ndoni et al (20) showed that hs-CRP was involved in the development of PE. Interaction between hydrogen peroxide and chloride ions can produce hypochlorite (HClO) to form MPO-H2O2-halogen system, and under the conditions of local defense response, MPO catalytic reaction can generate excessive oxidants to cause oxidative stress injury (21–23). In this study, serum MPO and hs-CRP levels were relatively high in patients with severe PE before treatment. After treatment with magnesium sulfate and compound Danshen injection, serum levels of MPO and HS-CRP decreased in all 4 groups. The decrease was more significant in early-onset and late-onset observation groups than in early-onset and late-onset control group, which was consistent with the study reported by Salonen et al (24), indicating that compound Danshen injection combined with magnesium sulfate can effectively reduce the level of MPO and HS-CRP in patients. Clinical effective rate and cure rate of early-onset observation group and late-onset observation group were higher than those of early-onset control group and late-onset control group. While improvement rate and invalid rate of early-onset observation group and late-onset observation group were lower than those of early-onset control group and late-onset control group, which further supported the conclusion that compound Danshen injection combined with magnesium sulfate can achieve better treatment outcomes than magnesium sulfate, which is consistent with the study reported by Alsuwaida et al (25).

This study is still limited by the small sample size, which may affect the results. More studies are needed to elucidate the pathogenesis of PE. Individualized comprehensive treatment of PE is needed to reduce the incidence of PE in China.

In conclusion, compound Danshen injection combined with magnesium sulfate can effectively reduce serum levels of MPO and hs-CRP, and improve patient's condition. The combined treatment can achieve better efficacy than magnesium sulfate alone.

 Acknowledgements

Not applicable.

 Funding

No funding was received.

 Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

 Authors' contributions

KY wrote this manuscript and helped with treatment of patients. KY and GD analyzed and interpreted serum levels of hs-CRP and MPO. JL contributed significantly to statistical analysis. All authors read and approved the final manuscript.

 Ethics approval and consent to participate

The study was approved by the Ethics Committee of The Second People's Hospital of Liaocheng (Liaocheng, China). Patients who participated in this research, signed the informed consent and had complete clinical data. Signed informed consents were obtained from the patients or guardians.

 Consent for publication

Not applicable.

 Competing interests

The authors declare that they have no competing interests.

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Comparison of general information between groups.

Items Early-onset observation group Early-onset control group Late-onset observation group Late-onset control group t-value P-value
Cases 125 125 125 125
Age (years) 27.5±2.6 26.9±3.1 29.5±2.4 28.7±2.7 0.79 0.59
Gestational age 31.7±1.6 30.8±1.5 37.2±2.1 37.9±1.7 11.79 0.002
Pre-pregnancy BMI (KG/M2) 19.5±1.6 18.6±2.1 18.3±1.4 19.3±1.8 0.88 0.49
Pregnancy BMI (KG/M2) 25.3±1.4 24.7±1.2 25.1±1.7 24.8±1.6 0.86 0.51
Blood pressure (mmHg)
  Systolic 160.2±5.5 159.7±4.9 161.2±5.7 160.8±5.3 0.66 0.67
  Diastolic 99.8±3.5 98.2±3.2 97.9±3.1 99.2±2.9 0.34 1.36
MAP (mmHg) 119.2±2.3 118.7±2.1 119.4±2.7 118.9±2.6 0.59 0.81
White blood cell count (×109/l) 10.3±2.4 10.7±2.6 8.4±2.1 8.1±2.7 9.56 0.019

Comparison of serum levels of MPO and hs-CRP before and after treatment.

Groups (n=125) Time-points hs-CRP (mg/l) MPO (ng/l)
Early-onset observation Before treatment 3.43±1.51 14.79±4.24
After treatment 1.22±0.43aΔ 10.75±1.31aΔ
Late-onset observation Before treatment 3.21±1.48 14.02±3.79
After treatment 1.04±0.52aΔΔ 10.22±1.02aΔΔ
Early-onset control Before treatment 3.64±1.69 16.53±4.72
After treatment 1.78±0.84a 14.28±1.53a
Late-onset control Before treatment 3.56±1.81 15.38±3.98
After treatment 1.82±0.56a 13.37±1.45a

Compared with the pre-treatment level within the same group (p<0.05); Δcompared with early-onset control group (p<0.05); ΔΔcompared with late-onset control group (p<0.05).

Comparison of clinical efficacy (n, %).

Groups Cases Cure Improvement Invalid Total effective rate (%)
Early-onset observation 125 54 (43.2) 64 (51.2) 7 (5.60) 94.4a
Early-onset control 125 28 (22.4) 71 (56.8) 26 (20.8) 79.2
Late-onset observation 125 49 (39.2) 63 (50.4) 13 (10.4) 89.6b
Late-onset control 125 24 (19.2) 73 (58.4) 28 (22.4) 77.6

Compared with early-onset control group (p<0.05)

compared with late-onset control group (p<0.05).