[关键词]
[摘要]
目的 比较小青龙汤配方颗粒及饮片汤剂治疗变应性鼻炎(AR)小鼠的有效性与安全性。方法 将 42 只 雌性 BALB/c 小鼠随机分为对照组、模型组、小青龙汤饮片低剂量组(11.83 g·kg-1 )、小青龙汤饮片高剂量组 (23.66 g·kg-1 )、小青龙汤颗粒低剂量组(3.61 g·kg-1 )、小青龙汤颗粒高剂量组(7.22 g·kg-1 )、地塞米松组 (1 mg·kg-1 ),每组 6 只。小鼠在第 1、6、11、16 天腹腔注射含 25 µg 鸡卵清蛋白(OVA)+2 mg 氢氧化铝的磷 酸盐缓冲液(PBS)200 µL, 造成基础致敏;于第 22 天至第 28 天,每天用含 25 µg·µL-1浓度 OVA 的 PBS(40 µL) 滴鼻 1 次(每侧鼻腔滴入 20 µL),连续滴鼻 1 周。每日滴鼻前 1 h,各给药组按照上述设定剂量灌胃给药,每 天 1 次,连续灌胃 1 周。在末次 OVA 溶液滴鼻后的 10 min 内,对小鼠进行打喷嚏、挠鼻次数统计;采用 HE 及 PAS 染色法观察小鼠鼻黏膜病理改变;采用 ELISA 法测定小鼠血清鸡卵清蛋白-特异性免疫球蛋白 E (OVA-sIgE)、白细胞介素 4(IL-4)、白细胞介素 5(IL-5)、白细胞介素 13(IL-13)水平;全自动生化分析仪 检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、肌酐(CREA)及尿素(UREA)水平。 结果 (1)与对照组比较,模型组小鼠的打喷嚏及挠鼻次数显著增加(P<0.01);小鼠鼻黏膜充血水肿,细胞排 列紊乱,杯状细胞增生数量显著增多(P<0.01);血清 OVA-sIgE、IL-4、IL-5、IL-13 水平均显著升高(P< 0.01)。与模型组比较,各给药组小鼠的挠鼻次数均显著减少(P<0.01),地塞米松组、小青龙汤颗粒及饮片高 剂量组的打喷嚏次数显著减少(P<0.05,P<0.01);各给药组小鼠的鼻黏膜充血水肿明显减轻,炎性细胞浸润 减少,杯状细胞数量显著减少(P<0.01),血清 OVA-sIgE、IL-4、IL-5、IL-13 水平均显著降低(P<0.01)。与 等生药量饮片组比较,小青龙汤颗粒低剂量组的挠鼻次数显著减少(P<0.01);小青龙汤颗粒低、高剂量组的 杯状细胞数量显著减少(P<0.05,P<0.01),血清 OVA-sIgE、IL-4、IL-5、IL-13 水平均显著降低(P<0.05, P<0.01)。(2)各组小鼠的肝、肾组织结构清晰,肝细胞形态正常,肾小球与肾小管的结构未见异常变化,血清 ALT、CREA、UREA 水平无明显差异(P>0.05)。与对照组比较,其余各组小鼠的血清 AST 水平均明显升高 (P<0.05,P<0.01);与模型组比较,各给药组小鼠的血清 AST 水平无明显差异(P>0.05)。结论 小青龙汤 配方颗粒和饮片汤剂均能有效缓解 AR 小鼠的鼻痒症状,改善鼻黏膜病理变化,降低血清变应性炎症因子水 平,配方颗粒的效果优于等生药量饮片汤剂。
[Key word]
[Abstract]
Objective To compare the efficacy and safety of dispensing granules and decoction pieces of Xiaoqinglong Decoction (XQLD) in treating allergic rhinitis (AR) in mice. Methods Forty-two female BALB/c mice were randomly divided into a control group,a model group,a low-dose XQLD decoction pieces group (11.83 g·kg-1 ),a high-dose XQLD decoction pieces group (23.66 g·kg-1 ),a low-dose XQLD dispensing granules group (3.61 g·kg-1 ), a high-dose XQLD dispensing granules group (7.22 g·kg-1 ),and a Dexamethasone group (1 mg·kg-1 ),with 6 mice in each group. Mice were intraperitoneally injected with 200 µL of phosphate-buffered saline (PBS) containing 25 µg ovalbumin (OVA) and 2 mg aluminum hydroxide on days 1,6,11,and 16 to induce basic sensitization. From day 22 to day 28,mice were intranasally administered 40 µL of PBS containing 25 µg·µL-1 OVA (20 µL per nostril) once daily for one week. One hour before each intranasal administration,the treatment groups were orally administered the corresponding doses once daily for one week. Within 10 minutes after the last OVA intranasal administration,the number of sneezes and nasal scratches was recorded. HE and PAS staining were used to observe pathological changes in the nasal mucosa. ELISA was used to measure serum levels of ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin-4 (IL-4),interleukin-5 (IL-5),and interleukin-13 (IL-13). An automatic biochemical analyzer was used to measure serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and urea (UREA) . Results (1) Compared with the control group, the number of sneezes and nasal scratches in the model group significantly increased (P<0.01); the nasal mucosa showed congestion, edema, disordered cell arrangement,and a significant increase in goblet cell hyperplasia (P<0.01);serum levels of OVAsIgE,IL-4,IL-5,and IL-13 significantly increased (P<0.01). Compared with the model group,the number of nasal scratches in all treatment groups significantly decreased (P<0.01), and the number of sneezes in the Dexamethasone group, high-dose XQLD dispensing granules group, and high-dose XQLD decoction pieces group significantly decreased (P<0.05, P<0.01); nasal mucosal congestion and edema were significantly alleviated, inflammatory cell infiltration decreased, and the number of goblet cells significantly decreased (P<0.01); serum levels of OVA-sIgE,IL-4,IL-5,and IL-13 significantly decreased (P<0.01). Compared with the equivalent crude drug dose decoction group,the number of nasal scratches in the low-dose XQLD dispensing granules group significantly decreased (P<0.01); the number of goblet cells in the low- and high-dose XQLD dispensing granules groups significantly decreased (P<0.05,P<0.01),and serum levels of OVA-sIgE,IL-4,IL-5,and IL-13 significantly decreased (P<0.05, P<0.01). (2) The liver and kidney tissues of mice in all groups showed clear structures, normal hepatocyte morphology,and no abnormal changes in glomerular and tubular structures. There were no significant differences in serum levels of ALT,CREA,and UREA (P> 0.05). Compared with the control group,serum AST levels in all other groups significantly increased (P<0.05,P<0.01);compared with the model group,there were no significant differences in serum AST levels in all treatment groups (P> 0.05). Conclusion Both dispensing granules and docoction pieces of XQLD can effectively alleviate nasal itching symptoms, improve nasal mucosal pathological changes,and reduce serum levels of allergic inflammatory factors in AR mice. The efficacy of dispensing granules is superior to that of the equivalent crude drug dose decoction.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金项目(82274590,82305325,82474584);广东省基础与应用基础研究基金项目(2023A1515220080,2021A1515110446, 2024A1515011440);广州市科技基础与应用基础研究项目(202201011211);广州市科技计划项目(202201020308,2023A03J0587);深圳市自然 科学基金面上项目(JCYJ20210324111205016);深圳三名工程“广州中医药大学第一附属医院阮岩教授中医五官科团队”(SZZYSM202311005); 广州市耳鼻咽喉科临床与基础研究重点实验室(2023A03J0521)