摘要
目的探讨活血行气类中药制剂川芎嗪与丹参酮ⅡA修复脊髓损伤的效果及机制。方法将48只雌性SD大鼠随机分为假手术组、模型组、川芎嗪组和丹参酮ⅡA组,每组12只。假手术组仅行椎板切除术,模型组、川芎嗪组和丹参酮ⅡA组采用自制显微双刃剪构建脊髓完全横断模型。术后30 min,川芎嗪组给予盐酸川芎嗪注射液25 mg/(kg·d)腹腔注射,丹参酮ⅡA组给予丹参酮ⅡA磺酸钠注射液20 mg/(kg·d)腹腔注射,假手术组和模型组均给予等量生理盐水腹腔注射,均1次/d,连续5 d。术后1,3,7,14 d采用BBB评分评估各组大鼠后肢运动功能;术后14 d,检测血液流变学指标和C反应蛋白水平,HE染色、Nissl染色、Masson染色观察脊髓组织病理形态,免疫组织化学染色观察脊髓组织中核因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)阳性表达情况。结果术后1 d、3 d、7 d、14 d,模型组、川芎嗪组、丹参酮ⅡA组大鼠BBB评分均明显低于假手术组(P均<0.05),模型组、川芎嗪组、丹参酮ⅡA组各时间点BBB评分比较差异均无统计学意义(P均>0.05)。术后14 d,川芎嗪组中切全血黏度与丹参酮ⅡA组高、中、低切全血黏度和血浆黏度均明显低于模型组(P均<0.05),且丹参酮ⅡA组中切全血黏度明显低于川芎嗪组(P<0.05);川芎嗪组与丹参酮ⅡA组血清C反应蛋白水平均明显低于模型组(P均<0.05),且川芎嗪组明显低于丹参酮ⅡA组(P<0.05)。HE染色显示,川芎嗪组、丹参酮ⅡA组炎性细胞数量较模型组显著减少;Nissl染色显示,川芎嗪组神经元数量多于丹参酮ⅡA组;Masson染色显示,川芎嗪组、丹参酮ⅡA组胶质瘢痕形成减少。川芎嗪组与丹参酮ⅡA组脊髓组织中NF-κB、TNF-α阳性表达平均光密度值均明显低于模型组(P均<0.05),IL-10阳性表达平均光密度值均明显高于模型组(P均<0.05);川芎嗪组NF-κB、TNF-α阳性表达平均光密度值均明显低于丹参酮ⅡA组(P均<0.05),IL-10阳性表达平均光密度值与丹参酮ⅡA组比较差异无统计学意义(P>0.05)。结论川芎嗪与丹参酮ⅡA均能有效修复脊髓损伤,机制可能与改善微循环、抑制炎症反应有关;川芎嗪在抑制炎症反应、保护神经元方面的效果优于丹参酮ⅡA。
Objective It is to explore the effect and mechanism of the traditional chinese medicine prepatations for activating blood and moving qi tetramethylpyrazine and tanshinoneⅡA in repairing spinal cord injury.Methods Forty-eight female SD rats were randomly divided into sham operation group,model group,tetramethylpyrazine group and tanshinoneⅡA group,with 12 rats in each group.Only laminectomy was performed in the sham operation group,while the complete spinal cord transection models were constructed with self-made microscopic double-edge scissors in the model group,tetramethylpyrazine group and tanshinoneⅡA group.At 30 min after surgery,tetramethylpyrazine group was given tetramethylpyrazine hydrochloride injection 25 mg/(kg·d)by intraperitoneal injection,the tanshinoneⅡA group was given tanshinoneⅡA sodium sulfonate injection 20 mg/(kg·d)by intraperitoneal injection,and both sham operation group and model group were given equal amount of normal saline by intraperitoneal injection,all once daily,continuously treated for 5 days.BBB score was used to evaluate the recovery of hind limb motor function at 1,3,7 and 14 days after operation.At 1,3,7 and 14 days after surgery,the motor function of the hind limbs of the rats in each group was assessed by BBB score;at 14 days after surgery,the levels of blood rheological indexes and C-reactive protein were measured,and the histopathological morphology of the spinal cord was observed by HE staining,Nissl staining and Masson staining,and the positive expressions of nuclear factor-κB(NF-κB),tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in spinal cord tissues were observed by immunohistochemical staining.Results At 1,3,7 and 14 days after surgery,the BBB scores of the rats in the model group,tetramethylpyrazine group and tanshinoneⅡA group were significantly lower than those in the sham operation group(all P<0.05),and there was no statistically significant difference in the BBB scores among the model group,tetramethylpyrazine group and tanshinoneⅡA group at each time point(all P>0.05).At 14 days after surgery,the mid-cut whole blood viscosity in the tetramethylpyrazine group and the high,medium and low-cut whole blood viscosity and plasma viscosity in the tanshinoneⅡA group were significantly lower than those in the model group(all P<0.05),and the mid-cut whole blood viscosity in the tanshinoneⅡA group was significantly lower than that in the tetramethylpyrazine group(P<0.05);the levels of serum C-reactive protein in the tetramethylpyrazine group and tanshinoneⅡA group were significantly lower than those in the model group(all P<0.05),and the level of serum C-reactive protein in the tetramethylpyrazine group were significantly lower than that in the tanshinoneⅡA group(P<0.05).HE staining showed that the number of inflammatory cells was significantly reduced in the tetramethylpyrazine and tanshinoneⅡA group compared with the model group;Nissl staining showed that the number of neurons was more in the tetramethylpyrazine group than that in the tanshinoneⅡA group;Masson staining showed that glial scar formation was reduced in the tetramethylpyrazine group and TanshinoneⅡA group.The mean optical density values of positive expression of NF-кB and TNF-αin the spinal cord tissues of the tetramethylpyrazine and tanshinone IIA group were significantly lower than those of the model group(all P<0.05),and the mean optical density values of positive expression of IL-10 were significantly higher than those of the model group(both P<0.05);the mean optical density values of positive expression of NF-кB and TNF-αin the tetramethylpyrazine group and tanshinone IIA group were significantly lower than those of the tanshinoneⅡA group(all P<0.05),and there was no significant difference in the mean optical density values of positive expression of IL-10 between the tetramethylpyrazine group and TanshinoneⅡA group(P>0.05).Conclusion Both tetramethylpyrazine and tanshinoneⅡA can effectively repair spinal cord injury,and the mechanism may be related to improving microcirculation and inhibiting inflammation.Tetramethylpyrazine was superior to tanshinoneⅡA in inhibiting inflammatory response and protecting neurons.
作者
蒋昇源
邓博文
刘港
陶经纬
范筱
赵毅
任敬佩
徐林
穆晓红
JIANG Shengyuan;DENG Bowen;LIU Gang;TAO Jingwei;FAN Xiao;ZHAO Yi;REN Jingpei;XU Lin;MU Xiaohong(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China;Qingdao Municipal Hospital,Qingdao 266000,Shandong,China)
出处
《现代中西医结合杂志》
CAS
2023年第9期1176-1182,共7页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
中国博士后科学基金面上资助项目(2022M710472)。
关键词
脊髓损伤
川芎嗪
丹参酮ⅡA
微循环
炎症反应
神经修复
spinal cord injury
tetramethylpyrazine
tanshinoneⅡA
microcirculation
inflammation
nerve repair
