目的 探究丹参与红花有效成分的不同配伍组方对大鼠脑缺血再灌注损伤的保护作用。方法 选取成年雄性SD大鼠，通过大脑中动脉线栓法建立脑缺血再灌注模型，随机分成假手术组、模型组、阳性对照组（丹红注射液2 mL/kg）以及采用正交试验法L₉（3⁴）对丹参与红花主要有效成分[丹参素、丹酚酸A、丹酚酸B、羟基红花黄色素A（HYSA）]剂量配伍9组。大鼠尾iv给药，每天1次，连续给药3 d后进行神经功能缺损评分；实时荧光定量PCR法检测大鼠大脑皮层中葡萄糖调控蛋白78（GRP-78）、核转录因子-κB p65（NF-κB p65）、内质网源性转录因子（CHOP）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）mRNA表达；HE染色检测大鼠大脑皮层病理变化；免疫组化法检测大鼠大脑皮层中NF-κB p65蛋白的表达情况。结果 与模型组比较，丹红注射液、丹参与红花主要有效成分配伍可显著降低脑缺血再灌注大鼠的神经功能评分，使大鼠大脑皮层GRP-78 mRNA表达水平升高，NF-κB p65、CHOP、TNF-a、IL-6 mRNA表达水平降低，抑制大脑皮层中NF-κB p65蛋白表达。丹参与红花主要有效成分配伍9组中第4组（丹参素30 mg/kg、丹酚酸A 2.5 mg/kg、丹酚酸B 16 mg/kg、HYSA 8 mg/kg）、第6组（丹参素30 mg/kg、丹酚酸A 10 mg/kg、丹酚酸B 8 mg/kg、HYSA 4 mg/kg）对大鼠脑缺血再灌注损伤的保护作用更为显著。结论 丹参与红花有效成分各配伍组方均能对脑缺血再灌注损伤大鼠内质网应激、炎症等方面起良好的保护作用。

Objective To explore the protective effects of Salvia miltiorrhiza and Carthamus tinctorius active ingredients in different compatibility on cerebral ischemia-reperfusion injury in rats. Methods Adult male Sprague-Dawley (SD) rats were selected to establish a cerebral ischemia-reperfusion (I/R) injury model by middle cerebral artery occlusion (MCAO) method. The rats were randomly divided into sham operation group, model group, and positive control group (Danhong Injection 2 mL/kg); And orthogonal test method L₉(3⁴) was adopted to compose nine compatibility groups from main active ingredients of S. miltiorrhiza and C. tinctorius (trashinol, salvianolic acid A, salvianolic acid B, and HYSA). Rats were tail iv administrated once daily for continuous 3 d. Score neurological deficit was evaluated after 3 d; qRT-PCR was used to detect mRNA expression of glucose regulated protein 78 (GRP-78), nuclear factor-κB (NF-κB), C/EBP homologous protein (CHOP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6); HE staining was used to detect the pathological changes of cerebral cortex, and the expression of NF-κB p65 protein in cerebral cortex was detected by immunohistochemistry. Results Compared to the model group, Danhong Injection group and orthogonal compatibility nine groups significantly reduced the neurological deficit scores of rats with cerebral ischemia-reperfusion; increased the mRNA expression of GRP-78 in the cerebral cortex; decrease the mRNA expression of NF-κB, CHOP, TNF-α, and IL-6, and decrease the protein expression of NF-κB p65 in the cerebral cortex. The results also showed that the protective effects of the 4th group (danshensu 30 mg/kg, salvianolic acid A 2.5 mg/kg, salvianolic acid B 16 mg/kg, and HYSA 8 mg/kg), 6th group (trashinol 30 mg/kg, salvianolic acid A 10 mg/kg, salvianolic acid B 8 mg/kg, and HYSA 4 mg/kg) in the 9th group were more significant for cerebral ischemia reperfusion injury in rats. Conclusion The active components of S. miltiorrhiza and C. tinctorius can play a good protective role in endoplasmic reticulum stress and inflammation in rats with cerebral ischemia reperfusion injury.

国家自然科学基金资助项目（81630105）；浙江省自然科学基金项目（LZ17H270001，LZ18H270001）