白花九里明对急性肝损伤小鼠的保护作用及机制

摘要

目的：探讨白花九里明提取液对急性肝损伤小鼠的保护作用及机制。方法取 KM小鼠50只，随机均分为5组，正常对照组和模型对照组给予0．9％ NaCl 注射液，联苯双酯组给予0．2 g／kg 联苯双酯，白花九里明低浓度组和高浓度组分别给予15、30 g／kg 的白花九里明提取液灌胃7 d；同时在灌胃的第1、3、5天，对正常对照组给予0．9％ NaCl 注射液腹腔注射，模型对照组、联苯双酯组、白花九里明低浓度和高浓度组均给予0．1％四氯化碳（CCl4）溶液腹腔注射。末次灌胃1 h 后，采血分离血清、取肝左叶制肝悬液分离上清液、取肝右叶制备组织切片。检测肝匀浆和血清的总蛋白（TP）含量、谷丙转氨酶（GPT）活性、谷草转氨酶（GOT）活性、超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量，镜下观察肝组织结构变化。结果模型对照组、联苯双酯组、白花九里明低浓度组肝匀浆TP 含量明显高于正常对照组（P 均＜0．01），白花九里明高浓度组肝匀浆 TP 含量明显高于正常对照组和模型对照组（P 均＜0．05），正常对照组、模型对照组、白花九里明低浓度组肝匀浆 GPT 活性明显高于联苯双酯组和白花九里明高浓度组（P 均＜0．05），白花九里明低浓度组血清 GOT 活性明显低于正常对照组（P ＜0．05）；白花九里明高浓度组、联苯双酯组、模型对照组肝匀浆 SOD 活性明显低于正常对照组（P 均＜0．05），白花九里明低浓度组的肝匀浆SOD 活性明显高于联苯双酯组（P ＜0．05），白花九里明低浓度组血清 SOD 活性明显高于正常对照组、模型对照组、联苯双酯组、白花九里明高浓度组（P 均＜0．01）；白花九里明低浓度组和高浓度组肝匀浆 MDA 含量明显低于正常对照组（P 均＜0．05）；其余各组血清 TP 含量、GPT 活性、GOT 活性、SOD 活性、MDA 含量组间两两比较差异无统计学意义（P 均＞0．05）。镜下示联苯双酯组、白花九里明低浓度组和高浓度组与模型对照组相比，肝组织结构清晰，肝细胞变性溶解坏死数量等均有较大改善，白花九里明低浓度组的少数中央静脉管腔内见少量的脱落肝组织结构。结论白花九里明对 CCl4诱导的急性肝损伤有明显的保护作用，且呈浓度依赖性，高浓度白花九里明保护肝细胞效应与联苯双酯相当；其机制可能与促进和调动 SOD 清除自由基、阻断和降低肝细胞的脂质过氧化反应、提高肝细胞蛋白质合成有关。%Objective To investigate the protective effect of Blumea megacephala extracting solution on acute liver injury of mice and its mechanism of action.Methods Fifty KMmice were randomly divided into 5 groups.Normal con-trol group and model control group were given 0.9% NaCl injection,bifendatatum group was given 0.2 g/kg bifendatatum, Blumea megacephala low-concentration group and high-concentration group were respectively given 15 and 30 g/kg Blumea megacephala extracting solution for 7 days by gastric irrigation.Meanwhile,on day 1,3 and 5 of gastric irrigation,the nor-mal control group was given 0.9% NaCl by intraperitoneal injection,the rest of the groups were given 0.1%Carbon tetra-chloride (CCL4 )liquid.One hour 1 h after the last intragastric administration,we collected and separated the serum,and took the left lobe of liver to make and separate the liver supernatant,took the right lobe of liver to make tissue section.The total protein (TP),glutamic-pyruvic transaminase (GPT),glutamic-oxalacetic transaminase (GOT),superoxide dis-mutase (SOD)and malondialdehyde (MDA)content or activity in liver homogenate and serum were detected and we ob-served the structure changes of liver tissue microscopically.Results The TP content of liver homogenate in the model con-trol group,bifendatatum group and Blumea megacephala low-concentration group was obviously higher than that of the nor-mal control group (all P <0.01).The TP content of liver homogenate in the Blumea megacephala high-concentration group was higher than that of the normal control group and model control group (all P <0.05).The GPT activity of liver homoge-nate in the normal control group,model control group and Blumea megacephala low-concentration group was higher than that of the bifendatatum group and Blumea megacephala high-concentration group (all P <0.05).The GOT activity of ser-um in the Blumea megacephala low-concentration group was lower than that of the normal control group (P <0.05).The SOD activity of liver homogenate in the Blumea megacephala high-concentration group,bifendatatum group and model con-trol group was lower than that of the normal control group (all P <0.05).The SOD activity of liver homogenate in the Blumea megacephala low-concentration group was higher than that of the bifendatatum group (P <0.05),but the SOD ac-tivity of serum was higher than that of the normal control group,model control group,bifendatatum group and Blumea megacephala high-concentration group (P <0.01).The MDA content of liver homogenate in the Blumea megacephala low-concentration group and high-concentration group was lower than that of the normal control group (all P <0.05).No statis-tically significant difference were found in the TP content,GPT activity,GOT activity,SOD activity and MDA content of serum among these groups (P >0.05).The histological examinations showed that the liver tissue structure was clear,less liver cells were degenerated,dissolved and necrotic and a small number of central venous cavities had a small amount of shedding liver tissue structure in the bifendatatum group,Blumea megacephala low-concentration and high-concentration group as compared with the model control group.Conclusions Blumea megacephala have protective effect on CCl4-in-duced acute liver injury with dose-effect relationship.The high-concentration Blumea megacephala have the same effect as bifendatatum on liver cells,whose mechanism may be related to facilitation and regulation of SOD in scavenging free radi-cals,blocking and reducing lipid peroxidation of liver cells,and enhancing protein synthesis in liver.