Institute of Neurology, China Three Gorges University, Yichang, Hubei Province, 443003, China.
Department of Neurology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei Province, 443003, China.
Chin J Integr Med. 2019 Apr;25(4):264-269. doi: 10.1007/s11655-018-2917-7. Epub 2018 Dec 28.
To evaluate the effect of Buyang Huanwu Decoction (, BYHWD) on glial scar after intracerebral hemorrhage (ICH) and investigate the underlying mechanism.
Collagenase type VII (0.5 U) was injected stereotaxically into right globus pallidus to induce ICH model. One hundred and twenty Sprague-Dawley rats were randomly divided into 3 groups according to a random number table, including normal group (n=40), ICH model group (n=40) and BYHWD group (n=40), respectively. After ICH, the rats in the BYHWD group were intragastrically administered with BYHWD (4.36 g/kg) once a day for 21 days, while the rats in ICH group were administered with equal volume of distilled water for 21 days, respectively. Double immunolabeling was performed for proliferating cell nuclear antigen (PCNA)/glial fibrillary acidic protein (GFAP) nuclei. The expression of GFAP and leukemia inhibitory factor (LIF) was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR).
The astrocytes with hypertrophied morphology around the hematoma was observed on day 3 after ICH. The number of GFAP positive cells and GFAP mRNA levels increased notably on day 3 and reached the peak on day 14 post-ICH (P<0.01). PCNA+/GFAP+ nuclei were observed around the hematoma and reached the peak on day 14 post-ICH (P<0.01). In addition, LIF-positive astrocytes and LIF mRNA level in the hemorrhagic region increased significantly till day 14 post-ICH (P<0.01). However, BYHWD not only reduced the number of PCNA/GFAP nuclei, but also decreased GFAP and LIF levels (P<0.05).
BYHWD could attenuate ICH-induced glial scar by downregulating the expression of LIF in the rats.
评价补阳还五汤(BYHWD)对脑出血(ICH)后胶质瘢痕的影响,并探讨其作用机制。
采用立体定位向右侧苍白球内注射胶原酶 VII(0.5 U)建立 ICH 模型。120 只 Sprague-Dawley 大鼠按随机数字表法分为正常组、ICH 模型组和 BYHWD 组,每组 40 只。ICH 后,BYHWD 组大鼠每日给予 BYHWD(4.36 g/kg)灌胃 21 天,ICH 组大鼠给予等容量蒸馏水灌胃 21 天。采用增殖细胞核抗原(PCNA)/胶质纤维酸性蛋白(GFAP)双免疫标记法检测 PCNA/GFAP 阳性细胞。采用免疫组化法和实时定量逆转录聚合酶链反应(RT-PCR)检测 GFAP 和白血病抑制因子(LIF)的表达。
ICH 后第 3 天,血肿周围可见形态肥大的星形胶质细胞。ICH 后第 3 天,GFAP 阳性细胞数和 GFAP mRNA 水平显著增加,于第 14 天达高峰(P<0.01)。血肿周围可见 PCNA/GFAP 阳性细胞核,于第 14 天达高峰(P<0.01)。此外,ICH 后第 14 天,出血区域 LIF 阳性星形胶质细胞和 LIF mRNA 水平明显增加(P<0.01)。但 BYHWD 不仅减少了 PCNA/GFAP 阳性细胞核数量,而且降低了 GFAP 和 LIF 水平(P<0.05)。
BYHWD 可通过下调大鼠 LIF 表达减轻 ICH 诱导的胶质瘢痕形成。