摘要
Objective:To verify the clinical efficacy and safety of Qufeng Tongxuan method in treating low- and moderate-volume intracerebral hemorrhage at acute stage.Methods:A prospective, multicenter, randomized, double-blind, placebo-controlled study was performed; patients with low- and moderate-volume intracerebral hemorrhage at the basal ganglia and/or thalamus accepted treatment in 16 hospitals from September 2019 to April 2022 were enrolled. These patients were divided into experimental and control groups with a block randomized method by SAS software. Patients in control group were given conventional western medicine treatment; those in experimental group accepted Qufeng Tongxuan method (sequential therapy of Shexiang Huayu Xingnao granules and Zhilong Huoxue Tongyu granules) besides conventional western medicine treatment. NIHSS was used to assess neurological function before treatment and on 7 th, 14 th, 30 th, and 90 th d of treatment. Prognoses of these patients were assessed by modified Rankin scale (mRS) before treatment and on 180 th d of treatment. Brain CT was performed before treatment and on 7 th and 14 th d of treatment to calculate the hematoma volume. Before treatment and on 14 th d of treatment, changes of coagulation function, liver and kidney functions of the 2 groups were compared. Adverse reactions during treatment in the 2 groups were recorded. Results:No significant differences in NIHSS scores were noted between the 2 groups before treatment, on 7 th, 14 th, and 30 th d of treatment ( P>0.05); NIHSS scores in experimental group on 90 th d of treatment were signficantly lower than those in control group ( P<0.05); NIHSS scores in experimental group decreased gradually before treatment and on 7 th, 14 th, 30 th and 90 th d of treatment, with statistical significances ( P<0.05). No significant differences in mRS scores were noted between the 2 groups before treatment ( P>0.05); mRS scores in experimental group on 180 th d of treatment were signfciantly lower than those in control group ( P<0.05). No significant difference in hematoma volume was noted between the 2 groups before treatment and on 7 th and 14 th d of treatment ( P>0.05); both groups had gradually decreased hematoma volumes before treatment and on 7 th and 14 th d of treatment, respectively, with significant differences ( P<0.05); the volume difference of hematoma between 14 th d of treatment and before treatment in experimental group (6.42[4.10, 11.73]) was significantly higher than that in control group (4.00[1.25, 10.58], P<0.05). No significant differences in liver and kidney function indexes or coagulation function indexes were noted between the 2 groups before treatment and on 14 th d of treatment ( P>0.05). Adverse reaction incidence was 9.52% ( n=12) in experimental group and 10.34% ( n=12) in control group, without statistical difference ( P>0.05). Conclusion:Under premise of conventional western medicine treatment, Qufeng Tongxuan method can promote hematoma absorption and improve neurological deficit symptoms in low- and moderate-volume intracerebral hemorrhage at acute stage, without obvious adverse reactions.
摘要
OBJECTVE To study the effects of Zhilong huoxue tongyu capsules on intracerebral hemorrhage ，long non-coding RNA（LncRNA）and its target genes in mice. METHODS Twenty-four male C 57BL/6 mice were randomly divided into sham operation group 1，model group 1 and Zhilong huoxue tongyu capsule low-dose and high-dose groups （0.35，1.40 g/kg）. Collagenase was injected into the caudate nucleus to construct the model of intracerebral hemorrhage. One hour after the operation ， the mice in each treatment group were given the corresponding medicinal solution ，and the mice in the sham operation group 1 and the model group 1 were given normal saline intragastrically ，once a day ，for 3 consecutive days. The morphological changes of the brain tissue of the mice in each group were observed by hematoxylin-eosin staining and Nissl staining. The protein and mRNA expression of interleukin- 1β（IL-1β）and tumor necrosis factor-α（TNF-α）in the brain tissue were detected by immunohistoche- mistry，Western blot and real-time quantitative polymerase chain reaction （PCR）. In addition ，9 of male C 57BL/6 mice were randomly divided into sham operation group 2，model group 2 and intervention group （Zhilong huoxue tongyu capsule 1.40 g/kg）. The mice were modeled and administered according to the above method ，and then the whole brain tissue of mice in E-mail：tanruizhi627@swmu.edu.cn each group was isolated ， total RNA was extracted and sequenced，followed by analyzing the different LncRNA. Gene ontology（GO）enrichment was performed to predict effective LncRNA and target genes ，and verified by real-time quantitative PCR. RESULTS Compared with model group 1，the brain tissue pathological damages were significantly improved in Zhilong huoxue tongyu capsule low-dose a nd high-dose groups ，and the IL -1β， TNF-α protein and mRNA expression in brain tissue were significantly decreased （P＜0.05）. Two effective LncRNAs were screened out. The results of in vivo verification test （LncRNA-Dlst-211 was highly expressed in model group 2，and significantly down-regulated after the intervention of Zhilong huoxue tongyu capsules ； LncRNA-Dlst-211 target genes Rps 6kl1 and LncRNA-MSTRG.8169.4 were expressed weakly in model group 2，and strongly up-regulated after intervention ）were consistent with the sequencing results. CONCLUSIONS Zhilong huoxue tongyu capsules can improve the brain injury and inflammatory response in intracerebral hemorrhage model mice ，and its mechanism may be related to down-regulating the expression of LncRNA-Dlst-211 and up-regulating the expression of LncRNA-MSTRG. 8169.4 and Rps 6kl1.