Résumé
Objective:To explore the efficacy of breaking blood expelling stasis method accelerates hematoma resolution after intracerebral hemorrhage (ICH) and its potential mechanism.Methods:63 ICH patients confirmed by computer tomography (CT) scan from August 2019 to February 2020 were selected as the research objects and randomly divided into control group ( n=29, routine treatment plus placebo) and observation group ( n=34, routine treatment plus breaking blood expelling stasis granules). The changes of neurological function and hematoma volume were observed before and after treatment. At the same time, the ICH rat model was constructed to observe the changes of neurobehavior and hematoma volume after the intervention of breaking blood expelling stasis granules. The expressions of peroxidase proliferator-activated-receptor γ(PPARγ), CD11b and CD36 in the surrounding tissues of hematoma were detected by Western blot on the third day after the intervention. Results:After two weeks of treatment, the National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume of the two groups decreased (all P<0.05), and the NIHSS score and hematoma volume of the observation group were significantly lower than those of the control group (all P<0.05). In addition, the changes of NIHSS score and hematoma volume in the observation group before and after treatment were significantly greater than those in the control group ( P<0.01). In animal experiments, the hematoma volume in the breaking blood expelling stasis group on the 14th day after ICH was significantly smaller than that in the ICH group [(9.8±4.9)mm 3 vs (17.6±6.4)mm 3,P<0.05], and the reduction of hematoma in the breaking blood expelling stasis group on the 7th and 14th day was significantly larger than that in the ICH group [(4.6±2.9)mm 3 vs (-2.1±1.6)mm 3, (14.3±3.8)mm 3 vs (4.2±2.8)mm 3, all P<0.01]. The percentage of right turn on 3rd, 7th and 14th day and the modified Neurological Severity Score (mNSS) on 7th and 14th day in the breaking blood expelling stasis group were lower than those in the ICH group (all P<0.05). Western blot analysis showed that the expressions of CD11b, CD36 and PPARγ in the breaking blood expelling stasis group on the third day after ICH were significantly higher than those in the ICH group (CD11b: 0.78±0.12 vs 0.49±0.11, P<0.05; CD36: 1.16±0.16 vs 0.80±0.11, P<0.05; PPARγ: 0.78±0.11 vs 0.37±0.10, P<0.01). Conclusions:Breaking blood expelling stasis can effectively accelerate intracerebral hematoma clearance and improve neurological outcome after ICH, and the mechanism maybe probably mediated by activating PPARγ and enhanced CD36, CD11b upregulation on microglia/macrophages, which resulting in facilitating erythrocyte endogenous phagocytosis.
Résumé
Objective To observe the clinical effects of breaking blood expelling stasis method of traditional Chinese medicine (TCM) combined with edaravone on patients with acute hypertensive intra-cerebral hemorrhage and preliminarily discuss its protection mechanism on this disease. Methods Ninety-two patients with hypertensive intra-cerebral hemorrhage within 72 hours after occurrence admitted to Zengcheng District People's Hosipital of Guangzhou from May 2013 to December 2017 were enrolled, they were divided into conventional therapy group and combined treatment of TCM and western medicine group by random numbers produced by a computer, 46 cases in each group. The conventional therapy group was treated with conventional therapy, and the combined treatment of TCM and western medicine group was treated with conventional therapy, additionally the treatment of Poxue Zhuyu decoction (the ingredients of the decoction: leech 10 g, gradfly 10 g, rhubarb 15 g, cattail pollen 5 g, trichosanthes fruit 10 g, radix notoginseng 5 g, colla plastri testudinis 10 g, grassleaf sweetflag rhizome 10 g, ground beetle 3 g, dried lacquer 3 g, peach seed 10 g) and edaravone for 10 days. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were tested by enzyme-linked immunosorbent assay (ELISA) before and 7 days after treatment in the two groups; and the differences in National Institutes of Health stroke scale score (NIHSS) before and 14 days, 90 days after treatment as well as the changes of brain edema around the hematoma 14 days after treatment were compared between the two groups, and the incidence of adverse reaction was observed. Results After treatment, the levels of TNF-α, IL-6 and intra-cerebral hemorrhage quantities in the two groups were all decreased compared with those before treatment, and the degrees of decrease of TNF-α and cerebral hemorrhage volume in combined treatment of TCM and western medicine group were more significant than those in the conventional treatment group [TNF-α (ng/L): 21.00±6.10 vs. 29.40±11.33, cerebral hemorrhage volume (mL): 5.23±0.60 vs. 8.50±0.64, both P <0.05]. The IL-6 in the two groups were recovered to approximately normal levels after the treatment (ng/L: 13.60±5.36 vs. 15.40±6.13, P > 0.05). With the prolongation of therapeutic time, the scores of NIHSS of the two groups were significantly lowered than those before treatment, and the degree of reduction in the combined TCM and western medicine group on 90 days after treatment was more obvious than that of the conventional treatment group (4.34±0.67 vs. 7.73±0.61, P < 0.05). The volumes of edema around hematomas were increased after treatment in the two groups, but the degree of increase in combined treatment of TCM and western medicine group was slower than that of the conventional group (cm3: 7.57±0.64 vs. 10.16±0.60, P < 0.05). There was no statistical significant difference in the incidence of adverse reactions in comparison between the combined treatment of TCM and western medicine group and conventional therapy group [18.2% (8/44) vs. 20.5% (9/44), P > 0.05]. Conclusions Using breaking blood expelling stasis and edaravone for treatment of acute hypertensive intra-cerebral hemorrhage can accelerate the absorption of brain hematoma and improve the neurological function, and its mechanism may be relevant to the inhibition of some inflammatory factors.