六神丸对非感染性、感染性炎症动物模型抗炎作用研究

Study on Anti-inflammatory Effects of Liushen Pills on Animal Models with Non-infective Inflammation and Infective Inflammation

目的考察六神丸(胶囊)对非感染性、感染性炎症动物模型的抗炎作用及其可能的机制。方法通过巴豆油致小鼠耳肿胀试验、醋酸致小鼠腹腔毛细血管通透性增高试验、角叉菜胶致大鼠足肿胀试验、大鼠棉球肉芽肿试验,观察六神丸(胶囊)对非感染性炎症模型的抗炎作用。感染性炎症模型采用甲型流感病毒滴鼻感染致小鼠病毒性肺炎模型,观察六神丸(胶囊)对小鼠血清炎症因子及肺组织病理形态的影响;采用金黄色葡萄球菌腹腔注射感染致小鼠死亡试验,观察六神丸(胶囊)对小鼠死亡的影响。结果六神丸(胶囊)剂量为48.75、24.38、12.19 mg/kg时可明显抑制巴豆油致小鼠耳肿胀和醋酸致小鼠腹腔毛细血管通透性增高;六神丸(胶囊)剂量为33.75、16.88 mg/kg时可显著抑制角叉菜胶致炎后4 h大鼠足肿胀,并明显减轻棉球肉芽肿质量。六神丸(胶囊)剂量为48.75、24.38 mg/kg时可明显降低甲型流感病毒致病毒性肺炎小鼠血清炎症因子白细胞介素-6含量,六神丸(胶囊)剂量为24.38 mg/kg时可明显降低小鼠血清炎症因子肿瘤坏死因子-α含量,与模型组比较差异有统计学意义(P<0.05);病理组织学显示,六神丸(胶囊)各剂量组小鼠肺组织炎症、水肿等病变较模型组均有不同程度改善,病变分级经秩和检验,六神丸(胶囊)高、中剂量组差异有统计学意义(P<0.05)。体外实验,六神丸(胶囊)对金黄色葡萄球菌、表皮葡萄球菌、肺炎克雷白氏菌、变形杆菌、大肠杆菌、绿脓杆菌有杀菌作用;体内试验,六神丸(胶囊)剂量为24.38 mg/kg对腹腔注射金黄色葡萄球菌致小鼠死亡有保护作用,死亡率降低,与细菌感染组比较差异有统计学意义(P<0.05)。结论六神丸(胶囊)对非感染性、感染性炎症动物模型均有抑制作用,其机制可能是通过降低炎症因子含量发挥其抗炎作用。

Objective To investigate the anti-inflammatory effects and possible mechanism of Liushen Pills（Capsules） on non-infective inflammatory models and infective inflammatory animal models. Methods The anti-inflammatory effects of Liushen Pills（Capsules） on the non-infective inflammation models were observed by the test of mouse ear swelling induced by croton oil, the test of increased capillary permeability in abdominal cavity induced by acetic acid in mice, the rat foot swelling test caused by carrageenan, and the rat cotton granuloma test. The model of viral pneumonia caused by influenza A virus nasal infection was used to observe the effects of Liushen Pills（Capsules） on the serum inflammatory factors and the pathological morphology of lung tissue. Liquid dilution method was used to observe the effects of Liushen Pills（Capsules） on bacteriostasis in vitro. Staphylococcus aureus was injected into the abdomen by intraperitoneal injection to infect mice to die. The effects of Liushen Pills（Capsules） on the death of mice were observed. Results When the dosages of Liushen Pills（Capsules） were 48.75, 24.38, and 12.19 mg/kg, Liushen Pills（Capsules） could significantly inhibit the mouse ear swelling induced by croton oil and the peritoneal capillary permeability in mice induced by acetic acid. When the dosages of Liushen Pills（Capsules） were 33.75 and 16.88 mg/kg, Liushen Pills（Capsules） could significantly inhibit the swelling of rat foot caused by carrageenan after 4 h inflammation and the weight of cotton granuloma. When the dosages of Liushen Pills（Capsules） were 48.75 and 24.38 mg/kg, Liushen Pills（Capsules） could significantly decrease the content of inflammatory factor IL-6 caused by influenza A virus nasal infection. When the dosage of Liushen Pills（Capsules） was 24.38 mg/kg, Liushen Pills（Capsules） could significantly decrease the content of TNF-α in the serum. All of the above data showed statistical significance compared with the model group（P〈0.05）. Histopathology showed that the lesions of inflammation, swelling, and other pathology phenomena of lung tissue in mice with different dosages of Liushen Pills（Capsules） were improved compared with the model group. The graded lesions were tested by rank sum test, and there was statistical significance when Liushen Pills（Capsules） high-and medium-dosage groups（P〈0.05）. In vitro experiment showed that Liushen Pills（Capsules） had bactericidal effects on Staphylococcus aureus, Staphylococcus epidermidis, klebsiella pneumoniae, proteus, Escherichia coli and Pseudomonas aeruginosa. In vivo experiment showed that when the dosage of Liushen Pills（Capsules） was 24.38 mg/kg, Liushen Pills（Capsules） had protective effects on the death of mice induced by intraperitoneal injection of Staphylococcus aureus, and the death rate was lower, with statistical significance compared with the bacterial infection group（P〈0.05）. Conclusion Liushen Pills（Capsules） has inhibitory effects on non-infective inflammation and infective inflammation animal models, and its mechanism may play an anti-inflammatory role by reducing inflammatory factors.