机构地区:[1]中国中医科学院望京医院病理科,北京100102 [2]北京中医药大学研究生院,北京100029 [3]中国中医科学院望京医院脊柱二科,北京100102 [4]中国中医科学院望京医院学术发展处,北京100102 [5]中国中医科学院望京医院超声科,北京100102
出 处:《中国药物警戒》2025年第3期249-257,共9页Chinese Journal of Pharmacovigilance
基 金:国家自然科学基金资助项目(82174415、82405441、82205151);中国中医科学院望京医院高水平中医医院建设项目中医药临床循证研究专项(WJYY-XZKT-2023-25);中国中医科学院科技创新工程(CI2021A05054)。
摘 要:目的探究补肾活血方对大鼠肾虚血瘀型腰椎间盘退变的干预作用。方法36只SD大鼠随机分为假手术组,模型组,美洛昔康组(0.135 mg·kg^(-1)),补肾活血方低、中、高剂量组(2.97、5.94、11.88 g·kg^(-1)),每组6只。采用腰椎动静力失衡法建立腰椎间盘退变模型,采用肌内注射氢化可的松联合皮下注射肾上腺素构建肾虚血瘀模型,腰椎X线、番红O-固绿(SO/FG)染色观察大鼠椎间盘组织病理形态变化;免疫组织化学(IHC)染色观察大鼠椎间盘软骨终板Ⅱ型胶原蛋白(COL2A1)、聚集蛋白聚糖(ACAN)等蛋白质的表达;检测大鼠血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、尿素氮(BUN)和肌酐(CREA)含量,计算肝肾脏器系数,苏木素-伊红(HE)染色观察肝肾组织病理变化。结果补肾活血方可以延缓大鼠椎间盘退变,增加软骨终板中COL2A1、ACAN、BCL-2、RGCC表达,降低BAX表达。血清ALT、AST、BUN、CREA的含量、肝肾脏器系数及肝肾HE染色未见明显异常。结论补肾活血方对大鼠肾虚血瘀型腰椎退变具有改善作用,可延缓椎间盘软骨终板的退变,可能通过促进软骨终板中Ⅱ型胶原和聚集蛋白聚糖的表达、抗凋亡及调控细胞周期发挥作用,且长期干预肾虚血瘀型腰椎间盘退变相对安全。Objective To explore the effect of interventions of Bushen Huoxue decoction in lumbar intervertebral disc degeneration with kidney deficiency and blood stasis in rats.Methods Thirty-six SD rats were randomly divided into the sham operation group,model group,meloxicam group(0.135 mg·kg^(-1)),and low,medium and high dose groups of Bushen Huoxue decoction(2.97、5.94、11.88 g·kg^(-1)),with 6 rats in each group.A lumbar disc degeneration model was established via lumbar dynamic and static imbalance while the model of kidney deficiency and blood stasis was established via intramuscular injection of hydrocortisone and subcutaneous injection of epinephrine.The pathomorphological changes of the lumbar intervertebral disc were observed by X-ray and safranine O-fast green(SO/FG)staining.The expressions of collagen type Ⅱ(COL2A1),aggrecan(ACAN)and other proteins in the cartilage endplate of intervertebral discs of rats were observed by immunohistochemical(IHC)staining.The contents of serum glutamic oxalic aminotransferase(AST),alanine aminotransferase(ALT),urea nitrogen(BUN)and creatinine(CREA)were detected,the organ coefficients of the liver and kidney were calculated,and the pathological changes of liver and kidney tissues were observed by hematoxylin-eosin(HE)staining.Results Bushen Huoxue decoction could delay the degeneration of the intervertebral disc in rats,increase the expressions of COL2A1,ACAN,BCL-2 and RGCC in the cartilage endplate,and decrease the expression of BAX.The contents of serum ALT,AST,BUN and CREA as well as the organ coefficients and HE staining of the liver and kidney remained normal.Conclusion Bushen Huoxue decoction can not only help improve lumbar degeneration with kidney deficiency and blood stasis in rats,but delay the degeneration of the cartilage endplate of the intervertebral disc.This decoction can promote the expressions of collagen type II and aggrecan in the cartilage endplate,inhibit apoptosis and regulate cell cycle.It is safe for long-term interventions in lumbar intervertebral
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