目的 通过小鼠全身主动过敏实验（ASA）和被动皮肤过敏实验（PCA）评价注射用丹参多酚酸（SAFI）的致敏性。方法 ASA和PCA分别设阴性对照（0.9%氯化钠注射液）组、卵清白蛋白（OVA，阳性药，10 mg·kg⁻¹）组和SAFI（228、114、23、5、2 mg·kg⁻¹）组，致敏均采用ip给药方式，隔天致敏1次，共致敏5次。末次致敏14 d后，ASA先取每组10只小鼠iv 2倍致敏剂量药液激发，30 min后眼内眦取血离心，ELISA法检测血清中肿瘤坏死因子-α（TNF-α）、组氨酸（His）、白细胞介素（IL）-10、血管内皮生长因子（VEGF）和β-氨基己糖苷酶（β-Hex）含量，肺组织苏木精-伊红（HE）染色后进行病理观察；另外每组10只iv 2倍致敏剂量药液混合0.4%伊文思蓝（EB）激发，30 min后记录各组耳廓蓝染和伊文思蓝渗出情况。PCA致敏后首先取血检测血清免疫球蛋白E（IgE）含量，剩余各组血清混匀后另取每组6只进行被动致敏测定背部蓝斑大小。结果 ASA结果显示，与阴性对照组相比，OVA组有明显过敏反应，SAFI 114、228 mg·kg⁻¹剂量（临床等效剂量的10、20倍）诱发耳廓蓝染过敏反应，其他剂量组均无明显过敏反应症状；肺部HE结果显示，与阴性对照组相比，OVA组肺泡壁凝固性坏死，肺间质有大量炎症因子浸润，激发后小鼠血清中His、VEGF、TNF-α、β-Hex释放量著升高（P＜0.001），IL-10释放量显著降低（P＜0.001），SAFI 228 mg·kg⁻¹组His含量显著升高（P＜0.001），其他生化指标均无显著性差异。PCA结果显示，仅OVA组小鼠背部可见明显蓝斑；仅OVA组致敏小鼠血清中IgE含量明显升高（P＜0.001）。结论 SAFI未产生由特异性抗体IgE介导的I型过敏反应，高剂量时可能会导致血管通透性增加。建议临床严格参照说明书，在安全剂量范围内使用，以降低不良反应发生率。

Objective The sensitization of Salvianolic Acids for Injection (SAFI) was evaluated by active systemic anaphylaxis (ASA) and passive cutaneous anaphylaxis (PCA) in mice. Methods Negative control (0.9% sodium chloride injection), ovalbumin (OVA, positive drug, 10 mg·kg⁻¹), and SAFI (228, 114, 23, 5, and 2 mg·kg⁻¹) were set up for ASA and PCA, respectively. Sensitization was performed by ip administration, every other day, for a total of five times. Fourteen days after the last sensitization, ASA first took 10 mice/group to be sensitized withiv two-fold sensitizing dose, and then centrifuged the blood from the inner canthus of the eyes after 30 min, and then detected the levels of tumor necrosis factor-α (TNF-α), histidine (His), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and β - glucosidase (β-Hex) in the serum by ELISA, and the lung tissue was observed by HE; and 10 mice/group were also sensitized with iv 2-fold sensitizing dose of the drug mixed with 0.4% Evans' Blue (EB), after 30 min, the auricular blue staining and EB exudation of each group were recorded. PCA firstly, blood was taken to detect serum IgE content, and the remaining sera of each group were mixed well and then another 6 mice were taken to determine the size of the blue spot on the back by passive sensitization.Results ASA results showed that compared with the negative control group, the OVA group had a significant allergic reaction, and the SAFI (114, 228 mg·kg⁻¹) group had induced an allergic reaction with blue staining of the auricle, while all other dose groups had no significant symptoms of allergic reaction; HE results of the lungs showed coagulative necrosis of the alveolar wall and a large amount of inflammatory factor infiltration of the interstitium of the lungs in the OVA group, and the serum of the mice after excitation, when compared with the negative control group. There were significant differences in the levels of TNF-α, IL-10, VEGF and β-Hex in the serum of mice after excitation (P < 0.001), and the level of His was significantly increased in the SAFI group at the highest dose of 228 mg·kg⁻¹, while other biochemical indexes did not show any significant differences. The results of PCA showed that only in the back of the mice in the OVA group, a clear blue spot could be seen; and the serum level of IgE was significantly elevated (P < 0.001) only in the OVA group of the sensitized mice. IgE content in the serum of sensitized mice in the OVA group only was significantly elevated (P < 0.001). Conclusion SAFI did not produce a type I allergic reaction mediated by the specific antibody IgE, and that the high dose may lead to an increase in vascular permeability. It is recommended that clinical use should be strictly referred to the instructions to reduce clinical adverse reactions.

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