黄桷树叶总黄酮提取物对脓毒症小鼠肝、肺的保护作用研究

Protective Effect of Total Flavonoids Extract from the Leaves of Ficus lacor on Liver and Lung of Mice with Sepsis

摘要: 目的：了解不同浓度黄桷树叶总黄酮提取物(FLA)对脂多糖(LPS)诱导的脓毒症小鼠肝、肺损伤的保护作用。方法：将SPF级C57/6J雄性小鼠随机分成对照组(CON组)、LPS模型组(LPS组)、LPS + 40 mg/kg FLA组(LPS + FLA-L组)和LPS + 80 mg/kg FLA组(LPS + FLA-H组)，每组6只。适应性喂养一周，再分别灌胃生理盐水和不同浓度FLA一周后，CON组腹腔注射PBS缓冲液，其余组均腹腔注射10 mg/kg LPS诱导建立脓毒症小鼠模型，腹腔注射12小时后进行血清和肝、肺组织的收集。ELISA检测血清中炎症因子IL-6和TNF-α的含量；HE染色观察肝、肺组织的病理情况；试剂盒检测血清ALT和AST水平；RT-qPCR检测肝、肺组织中炎症因子水平。结果：LPS + FLA-L组和LPS + FLA-H组均能逆转LPS导致的血清促炎因子IL-6 (从507.00 ± 121.43降至348.46 ± 87.65和310.13 ± 68.62 pg/ml)和TNF-α (从364.60 ± 68.60降至245.22 ± 58.94和192.14 ± 35.85 pg/ml)的升高(n = 4, P < 0.05)，减轻肝、肺组织的病理损伤，降低血清ALT(从168.42 ± 38.21降至111.62 ± 34.86和94.58 ± 19.96U/L)和AST (从361.32 ± 56.99降至250.01 ± 57.50和225.01 ± 61.79U/L)水平(n = 4, P < 0.05)，下调肝、肺组织的促炎因子(IL-1β、IL-6、IL-8和TNF-α)水平(n = 6, P < 0.05)，除了LPS + FLA-L组和LPS组的肺组织TNF-α水平之间没有统计学意义(n = 6, P > 0.05)。结论：黄桷树叶总黄酮提取物能有效改善LPS诱导的脓毒症小鼠炎症失衡和肝、肺损伤。

Abstract: Objective: To investigate the protective effects of different concentrations of total flavonoids extract from the leaves of Ficus lacor (FLA) on liver and lung injury induced by lipopolysaccharide (LPS) in mice with sepsis. Methods: SPF grade C57/6J male mice were randomly divided into control group (CON group), LPS model group (LPS group), LPS + 40 mg/kg FLA group (LPS + FLA-L group) and LPS + 80 mg/kg FLA group (LPS + FLA-H group), with 6 mice in each group. After one week of adaptive feeding, and then one week of intragastric administration of normal saline and different concentrations of FLA, CON group was intraperitoneally injected with PBS buffer, and other groups were intraperitoneally injected with 10 mg/kg LPS to induce the establishment of sepsis mouse model. Serum, liver and lung tissues were collected 12 hours after intraperitoneal injection. Serum levels of inflammatory cytokines IL-6 and TNF-α were detected by ELISA. The pathological conditions of liver and lung were observed by HE staining. Serum ALT and AST levels were detected by the kit. The levels of inflammatory factors in liver and lung tissues were detected by RT-qPCR. Results: Both LPS + FLA-L and LPS + FLA-H groups could reverse the increase of serum pro-inflammatory factors IL-6 (reduced from 507.00 ± 121.43 to 348.46 ± 87.65 and 310.13 ± 68.62 pg/ml) and TNF-α (reduced from 364.60 ± 68.60 to 245.22 ± 58.94 and 192.14 ± 35.85 pg/ml) induced by LPS (n = 4, P < 0.05), alleviate the pathological injury of liver and lung tissue, reduce the levels of serum ALT (reduced from 168.42 ± 38.21 to 111.62 ± 34.86 and 94.58 ± 19.96 U/L) and AST (reduced from 361.32 ± 56.99 to 250.01 ± 57.50 and 225.01 ± 61.79 U/L) (n = 4, P < 0.05), and down-regulated the levels of proinflammatory factors (IL-1β, IL-6, IL-8 and TNF-α) in liver and lung tissue (n = 4, P < 0.05), there was no statistical significance between TNF-α levels in lung tissues except LPS + FLA-L and LPS groups (n = 6, P > 0.05). Conclusion: The total flavone extract from leaves of Ficus virens can effectively improve the inflammation imbalance and liver and lung injury induced by LPS in mice with sepsis.