目的 通過小鼠全身主動過敏實驗（ASA）和被動皮膚過敏實驗（PCA）評價注射用丹參多酚酸（SAFI）的致敏性。方法 ASA和PCA分別設陰性對照（0.9%氯化鈉注射液）組、卵清白蛋白（OVA，陽性藥，10 mg·kg⁻¹）組和SAFI（228、114、23、5、2 mg·kg⁻¹）組，致敏均采用ip給藥方式，隔天致敏1次，共致敏5次。末次致敏14 d后，ASA先取每組10只小鼠iv 2倍致敏劑量藥液激發(fā)，30 min后眼內(nèi)眥取血離心，ELISA法檢測血清中腫瘤壞死因子-α（TNF-α）、組氨酸（His）、白細胞介素（IL）-10、血管內(nèi)皮生長因子（VEGF）和β-氨基己糖苷酶（β-Hex）含量，肺組織蘇木精-伊紅（HE）染色后進行病理觀察；另外每組10只iv 2倍致敏劑量藥液混合0.4%伊文思藍（EB）激發(fā)，30 min后記錄各組耳廓藍染和伊文思藍滲出情況。PCA致敏后首先取血檢測血清免疫球蛋白E（IgE）含量，剩余各組血清混勻后另取每組6只進行被動致敏測定背部藍斑大小。結(jié)果 ASA結(jié)果顯示，與陰性對照組相比，OVA組有明顯過敏反應，SAFI 114、228 mg·kg⁻¹劑量（臨床等效劑量的10、20倍）誘發(fā)耳廓藍染過敏反應，其他劑量組均無明顯過敏反應癥狀；肺部HE結(jié)果顯示，與陰性對照組相比，OVA組肺泡壁凝固性壞死，肺間質(zhì)有大量炎癥因子浸潤，激發(fā)后小鼠血清中His、VEGF、TNF-α、β-Hex釋放量著升高（P＜0.001），IL-10釋放量顯著降低（P＜0.001），SAFI 228 mg·kg⁻¹組His含量顯著升高（P＜0.001），其他生化指標均無顯著性差異。PCA結(jié)果顯示，僅OVA組小鼠背部可見明顯藍斑；僅OVA組致敏小鼠血清中IgE含量明顯升高（P＜0.001）。結(jié)論 SAFI未產(chǎn)生由特異性抗體IgE介導的I型過敏反應，高劑量時可能會導致血管通透性增加。建議臨床嚴格參照說明書，在安全劑量范圍內(nèi)使用，以降低不良反應發(fā)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.

R285.5

天津市制造業(yè)高質(zhì)量發(fā)展專項資金—天津天士力之驕藥業(yè)有限公司技術(shù)中心創(chuàng)新能力建設（ZZY20232088）