Effect of Xingnaojing Injection on inflammatory cytokines and blood coagulation function in patients with acute cerebral hemorrhage

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Effect of Xingnaojing Injection on inflammatory cytokines and blood

coagulation function in patients with acute cerebral hemorrhage

Zhen-Bing Cai

1

, Ying-Hua Huang

2

, Ting-Kai Jiang

1 1. Department of Neurology, Laibin People's Hospital, Sichuan, Laibin 546100, China

2. Department of Rehabilitation Medicine, Laibin People's Hospital, Sichuan, Laibin 546100, China

Journal of Hainan Medical University

http://www.hnykdxxb.com

ARTICLE INFO ABSTRACT

Article history:

Received 25 Oct 2017

Received in revised form 28 Oct 2017 Accepted 2 Nov 2017

Available online 14 Nov 2017

Keywords:

Xingnaojing injection Acute cerebral hemorrhage Inflammatory cytokines Coagulation function

Corresponding author: Huang Yinghua, Department of Rehabilitation Medicine, Laibin People's Hospital, Sichuan, Laibin 546100, China.

E-mail: caizhenbing276@163.com.

Fund Project: Scientific Research Project of Sichuan Provincial Science and Technology Department (No. 0152319).

1. Introduction

Cerebral hemorrhage (ICH) refers to the bleeding caused by angiorrhexis of non-traumatic brain parenchyma, which is mainly associated with cerebrovascular disease, and the death rate in acute stage is very high[1,2]. Changes of hematoma around the

local vascular circulation after cerebral hemorrhage, destruction of blood-brain barrier, high inflammatory response are closely related to the pathological process of cerebral hemorrhage, thus improving abnormal blood coagulation, reducing the release of inflammatory factors, thereby reduced secondary brain injury, which had important treatment value[3]. Xingnaojing with effect of promoting Qi, had a better effect on cerebral hemorrhage[4]. This article discussed the effect of Xingnaojing injection on coagulation function and inflammatory factors in patients with acute cerebral hemorrhage. The report was as follows.

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2. Data and methods

2.1 General data

All cases were obtained from patients with acute cerebral hemorrhage who were admitted in the Laibin City People's Hospital from October 2015 to May 2017. 80 patients were randomly divided into observation group and control group, each group contained 40 cases. The observation group: 22 males, 18 females, aged from 44 to 76 years; control group: 19 males and 21 females, aged from 47 to 78 years old. There was no significant difference in general data between the two groups (P>0.05).

Inclusion criteria: (1) met the diagnostic criteria of acute cerebral hemorrhage[5], diagnosed through the head CT or magnetic resonance imaging (MRI) examination; admitted in hospital within 24 h after attacking; amount of brain or basal ganglia hemorrhage was less than 30 mL; amount of cerebellum or thalamus bleeding was less than 10 mL; patients or their families agreed to participate in this study and signed informed consent.

Exclusion criteria: did not meet the diagnostic criteria; condition of disease aggregated severely within 48 h after admission, accompanied by brain malignancies meanwhile; suffered from mental illness; accompanied by severe cardiovascular, liver, kidney, blood system diseases; allergy to test drug.

2.2 Treatment method

Patients in two groups were given symptomatic conventional treatment, including hemostasis, appropriate control of blood pressure, reducing intracranial pressure, nourishing brain cells and control of infection. Patients needed to surgery undergoing surgical removal of hematoma or decompression; patients with breathing difficulties conducted tracheal intubation or tracheotomy, mechanical ventilation. According to the specific condition, gave the two groups of patients with mannitol or glycerol fructose to reduce intracranial pressure; patients in observation group were given additionally Xingnaojing injection on this basis (Wuxi Shanhe Pharmaceutical Co., Ltd., Approval number Z32020563): 20 mL of Xingnaojing injection liquid added in 250 mL, 0.9% of the saline intravenous for intravenous infusion, 1 time/d, during the treatment, forbade raw, cool, spicy food and smoking and drinking, and told the patient to maintain emotional stability. 7 d for a course of treatment, two groups of patients were treated for two courses.

2.3 Observe indicators

Before and after treatment, collected with 6 mL of venous blood after 8 h of fasting, and centrifuged at 3 000 r/min for 5 min in a high-speed centrifuge within 30 min. Then obtained serum to detect levels of TNF-α, hs-CRP and IL-10 by enzyme-linked immunosorbent assay (ELISA). The kit was provided by Beijing Bangbian Biomedical Company. Obtained serum to detect blood coagulation indexes by German BE coagulation test instrument, including activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib), thrombin time (TT) and D-dimerization (DD), all the used reagents adopting original matching kits.

2.4 Statistic analysis

The data were analyzed by SPSS 17.0 statistical software. In this study, the levels of TNF-α, hs-CRP, IL-10 and coagulation function were all conformed to normal distribution, presented as (Mean ± SD). Comparison of intergroup and intragroup was carried out t test. The difference was significant presented as P<0.05.

3. Results

3.1 Comparison of inflammatory cytokines

There was no significant difference in the levels of TNF-α, hs-CRP and IL-10 between the two groups before treatment (P>0.05). After treatment, the levels of TNF-α and hs-CRP in the two groups were significantly lower than those before treatment (P<0.05), while the levels of IL-10 were significantly higher than before treatment (P<0.05). after treatment the level of TNF-α (30.77 ± 10.27) ng/ L in the observation group was significantly lower than that in the control group (52.42 ± 11.95) ng/L, hs-CRP level (6.84 ± 2.27) ng/L was significantly lower than that in the control group (14.72 ±4.61) ng/L, IL-10 level (66.19 ± 5.07) ng/L was significantly higher than that in the control group (63.19 ± 6.55) ng/L; Differences in each group were statistically significant (P <0.05). As shown in Table 1.

Table 1.

Comparison of inflammatory cytokines in two groups before and after treatment (n=40).

Group Time TNF-α (ng/L) hs-CRP (mg/L) IL-10 (ng/L)

Control group Before

treatment 88.54±26.34 31.61±8.41 52.85±23.71 After

treatment 52.42±11.95* 14.72±4.61* 63.19±6.55* O b s e r va t i o n

group treatment Before 89.21 ±28.51 33.21±8.63 51.17±22.95 After

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3.2 Comparison of coagulation function indexes

There was no significant difference in APTT, PT, TT, Fib and DD levels between the two groups before treatment (P>0.05). After treatment, the levels of APTT, Fib and DD in the control group were significantly increased (P<0.05). The levels of PT and DD were significantly decreased and the level of Fib were significantly increased (P<0.05). Comparison of intergroup, the levels of APTT, PT and DD in the observation group were significantly lower than those in the control group, Fib level in observation group was obviously higher than control group, the difference was significant (P<0.05). There was no significant difference in TT level of intragroup and intergroup before and after treatment (P>0.05). As shown in Table 2.

4. Discussions

The incidence of cerebral hemorrhage is severe, the pathological mechanism is related to the ischemic edema around the lesion. The direct oppression and the space occupying effect of the hematoma can cause secondary brain injury, which is an important factor affecting the condition of disease[6,7]. A large area of edema occurred around the hematoma after 1-3 d of intracerebral hemorrhage and triggered a series of inflammatory responses, which was one of the major causes of secondary brain injury[8,9]. Therefore, the prevention and treatment of brain edema after cerebral hemorrhage and relieving the inflammatory response caused by the treatment of cerebral hemorrhage were one of the important measures. Studies have shown that abnormal blood coagulation after cerebral hemorrhage was also one of the critical factors leading to secondary brain injury, which led to hypercoagulable state and appeared hypercholesterolemia, extremely easily caused thrombosis, thereby resulting in secondary bleeding[10,11]. At present, treatment of cerebral hemorrhage in clinic commonly used Xingnaojing injection, because of its effect of promoting blood circulation, inducing resuscitation, eased brain edema after cerebral hemorrhage through the blood-brain barrier, thereby improved injury on nerve caused by hematoma, promoted the recovery of neurological function in patients[12]. Xingnaojing

prescription[13,14] is from Angong Niuhuang pills, consists of musk, radix curcumae, borneol, cape jasmine and other active ingredients. Among them, musk has effect of inducing resuscitation, removing stasis and promoting circulation, which can increase the excitement of central nervous system, improve brain function; Radix curcumae can cool blood and clear away the heart-fire and relieve pain; borneol is able to remove stasis and promote the micro-circulation, which can assist musk to enhance the awakening effect; cape jasmine can remove heat and cool blood, purge triple energizer merdian fire; four drugs combined, can play roles in refreshing resuscitation, purging pathogenic fire and detoxification, reducing phlegm and promoting blood circulation and others, suiting for acute fever syndrome. Modern pharmacological studies[15] showed that Xingnaojing injection can protect nerves and vascular endothelial cells, improve blood microcirculation, dilate blood vessels, inhibit inflammation, with effect of reducing vascular resistance, decreasing the role of nerve cell damage, which can thereby reduce the brain tissue edema and improve the metabolism level of hypoxia brain cells, and enhance cell tolerance to hypoxia, thus reducing brain edema and nerve cell damage, and promoting the recovery of brain function. Studies showed that[16,17], brain hematoma after cerebral hemorrhage would press surrounding tissue and lead to local ischemia and hypoxia, resulting in inflammatory response, inflammatory factor generated in this process can injury brain tissue, causing loss of neurological function in patients; at the same time, The formation of hematoma was also closely related to inflammation. TNF-α is a multifunctional inflammatory cytokine, closely associating to cerebrovascular disease, mainly generated in brain tissue neurons, stellate cells and oligodendrocytes, will promote inflammatory cell infiltration, aggregation, triggering inflammatory immune response, can induce sensitive cells to produce toxic effects, leading to the occurrence of cytotoxic brain edema[18]. hs-CRP is an inflammatory marker, which can indirectly reflect the degree of inflammatory response and tissue injury. IL-10 is mainly produced by monocyte macrophages, B lymphocytes or keratinocytes. The inflammatory response mainly plays negative regulation effect, can inhibit the secretion of TNF-α, IL-6 and chemokines by macrophages, and assist T cells[19]. This research found that the levels of TNF-α and hs-CRP in the two groups Table 2.

Comparison of coagulation function indexes in two groups before and after treatment (n=40).

Group Time APTT (s) PT (s) TT (s) Fib (g/L) DD (µg/L)

Control group Before treatment 27.09±5.31 14.51±2.27 15.27±3.84 3.24±1.32 3.29±2.26

After treatment 30.84±4.93* 14.27±3.02 15.22±3.67 4.64±1.23* 4.14±1.32*

Observation group Before treatment 26.91±4.21 14.21±2.36 15.67±3.12 3.07±1.09 3.41±2.19

After treatment 27.31±5.44# 12.72±3.11*# 14.94±3.01 5.25±0.72*# 0.49±0.14*#

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were significantly decreased and IL-10 level dramatically increased (P<0.05); and the change in observation group was more obvious than control group (P<0.05). The results showed that Xingnaojing injection notably reduced the levels of TNF-α and hs-CRP in blood of patients with acute cerebral hemorrhage and promoted the secretion of anti-inflammatory cytokines IL-10, which was more significant than routine therapy. The reason may be Xingnaojing injection can improve cerebral edema and hypoxia symptoms after cerebral hemorrhage, reduce the degree of brain damage deterioration, reduce the inflammatory response.

Coagulation dysfunction is one of the main factors that caused secondary brain injury after cerebral hemorrhage, seriously affect the prognosis, how to correct the abnormal coagulation function, improve the prognosis, is the difficult problem to domestic and foreign scholars[20,21]. Coagulation function indicators, APTT can reflect the lack of prothrombin and fibrinogen, is the comprehensive test indicators of endogenous coagulation system; PT can reflect the abnormal coagulation factors, is the comprehensive test indicators of external coagulation system; Fib is a thrombin substrate that can detect the formation of thrombus; DD is a specific fibrinolytic process marker, produced by the hydrolysis of fibrinolytic enzymes, and is used to detect the dissolution of fibrinolytic enzymes. The dissolution of fibrin and the formation of activated thrombus in the vessels may lead to increase of DD levels[22,23]. Studies demonstrated that[24], Xingnaojing injection through the blood-brain barrier, inhibit the over-expression of inflammatory factors, thereby reduced brain edema, intracranial pressure, promoted coagulation function to normal level. This study showed that APTT levels in the control group were significantly increased (P<0.05). APTT level in observation group was significantly lower than control group (P<0.05). The PT level in the control group was significantly increased after treatment (P<0.05). PT level in the observation group was significantly lower than that in the control group (P<0.05), moreover PT level in observation group was obviously lower than control group (P<0.05). After treatment, the levels of Fib in both groups were significantly higher than those before treatment, and the level of observation group was significantly higher than that of the control group (P<0.05). After treatment, DD level in the control group was significantly higher than that before treatment, while the level of DD in the observation group was significantly decreased, and DD level after treatment in observation group was dramatically lower than that in the control group (P<0.05). There was no significant difference in TT level between the two groups before and after treatment (P>0.05). The results revealed that Xingnaojing injection significantly improved the level of abnormal blood coagulation in patients with cerebral hemorrhage may be due

to the improvement of blood circulation, reducing blood pressure resistance, thereby relieved brain edema symptoms and inhibit formation of thrombus, thus regulated the balance of coagulation system, promoted coagulation function indexes to normal level. In conclusion, Xingnaojing injection can significantly alleviate the inflammatory response caused by cerebral hemorrhage, promote coagulation function indexes to normal level, thereby played a role in reducing brain damage and brain edema, worthy of clinical promotion.

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