五子衍宗方对环磷酰胺致肝损伤的保护作用及其机制研究
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摘要
目的研究五子衍宗方(WP)对环磷酰胺(CTX)致肝损伤的保护作用及其机制,以期为临床治疗提供借鉴。方法 2015年9月—2016年6月,将8周龄SPF级BALB/c雄性小鼠40只随机分为正常对照组、模型对照组、WP低剂量组、WP高剂量组,每组10只。应用WP提取黄酮类化合物并将其溶于1%羧甲基纤维素钠(CMCNa),WP低剂量组和WP高剂量组提前3 d分别给予黄酮类化合物140、280 mg/kg,灌胃给药30 d,1次/d;从第3天开始,除正常对照组腹腔注射等量0.9%氯化钠溶液外,其余各组均腹腔注射CTX 50 mg/kg造模,每隔2 d注射1次,共10次。模型对照组血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平与正常对照组比较有统计学差异提示造模成功。最后一次注射CTX 12 h后眼球取血、脱臼处死小鼠。检测血清ALT、AST水平;取肝脏,计算肝脏系数,HE染色法观察肝组织形态学表现,检测肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果模型对照组小鼠血清ALT、AST水平高于正常对照组(P<0.01);WP低剂量组、WP高剂量组小鼠血清ALT、AST水平低于模型对照组(P<0.05)。模型对照组肝脏系数高于正常对照组、WP低剂量组、WP高剂量组(P<0.01)。模型对照组小鼠肝小叶和肝索排列混乱,肝细胞肿胀明显并伴有坏死,胞质疏松。WP低剂量组、WP高剂量组肝小叶排列较整齐,肝细胞肿胀和胞质疏松程度较模型对照组明显减轻,肝细胞形态均匀,排列规整。模型对照组肝组织SOD水平低于正常对照组、WP低剂量组、WP高剂量组,MDA水平高于正常对照组、WP低剂量组、WP高剂量组(P<0.05)。结论 WP对CTX所致肝损伤具有良好的保护作用,其机制可能与提高机体的抗氧化能力,清除体内自由基有关。
Objective To study the protective effect and mechanism of Wuzi-Yanzong prescription( WP) against the liver injury induced by cyclophosphamide( CTX),so as to provide a reference for clinical treatment of the disease. Methods From September 2015 to June 2016,40 8-week-old SPF grade male BALB/c mice were randomly divided into normal control group,model control group,WP low-dose group,and WP high-dose group,with 10 mice in each. Flavonoids solution was made by dissolving the flavonoids extracted from WP in 1% CMC-Na. WP low-dose and high-dose groups were respectively intragastrically administered with flavonoids solution 140 mg/kg,280 mg/kg, once a day for 30 days from the 1st day of intervention. For modeling,from the 3rd day of intervention,mice in the control group were given intraperitoneal injection of0. 9% sodium chloride solution,while those in the other groups received intraperitoneal injection of CTX 50 mg/kg,once three days for 10 times. Successful modeling was considered when the levels of serum alanine aminotransferase( ALT) and aspartate aminotransferase( AST) in the model control group were statistically different from those in the normal control group. Twelve hours after the last time of injection,all the mice were sacrificed by cervical dislocation after taking blood from the eyeball. The serum levels of ALT and AST were detected, the liver was obtained to calculate the liver index, to observe the tissue morphology changes after HE staining and to determine the levels of superoxide dismutase( SOD) and malondialdehyde( MDA) in liver tissues. Results The serum ALT and AST levels in the model control mice were higher than those in the normal control group( P< 0. 01). The serum ALT and AST levels in the WP low-dose and high-dose groups were lower than those in the model control group( P < 0. 05). The liver index in the model control group was higher than that in the other 3 groups( P < 0. 01). In the model control group,the hepatic lobules and hepatic cords were disordered,and the hepatocytes were swollen and accompanied by necrosis and cytoplasm loose. However,in the WP low-dose and high-dose groups,liver lobules arranged neatly,liver cell swelling and cytoplasmic extent were significantly reduced compared with those in the model control group,liver cell morphology was uniform,and arranged in regular. The SOD level of liver tissue in the model control group was lower while the MDA level was higher than in the normal control group( P < 0. 01). WP low-dose group,WP high-dose group had higher SOD level but lower MDA level than the model control group( P < 0. 05). Conclusion WP has good protective effects on liver injury caused by CTX and its mechanism is probably related to the scavenging of free radical and increasing of cell anti-oxidative function.
Objective To study the protective effect and mechanism of Wuzi-Yanzong prescription( WP) against the liver injury induced by cyclophosphamide( CTX),so as to provide a reference for clinical treatment of the disease. Methods From September 2015 to June 2016,40 8-week-old SPF grade male BALB/c mice were randomly divided into normal control group,model control group,WP low-dose group,and WP high-dose group,with 10 mice in each. Flavonoids solution was made by dissolving the flavonoids extracted from WP in 1% CMC-Na. WP low-dose and high-dose groups were respectively intragastrically administered with flavonoids solution 140 mg/kg,280 mg/kg, once a day for 30 days from the 1st day of intervention. For modeling,from the 3rd day of intervention,mice in the control group were given intraperitoneal injection of0. 9% sodium chloride solution,while those in the other groups received intraperitoneal injection of CTX 50 mg/kg,once three days for 10 times. Successful modeling was considered when the levels of serum alanine aminotransferase( ALT) and aspartate aminotransferase( AST) in the model control group were statistically different from those in the normal control group. Twelve hours after the last time of injection,all the mice were sacrificed by cervical dislocation after taking blood from the eyeball. The serum levels of ALT and AST were detected, the liver was obtained to calculate the liver index, to observe the tissue morphology changes after HE staining and to determine the levels of superoxide dismutase( SOD) and malondialdehyde( MDA) in liver tissues. Results The serum ALT and AST levels in the model control mice were higher than those in the normal control group( P< 0. 01). The serum ALT and AST levels in the WP low-dose and high-dose groups were lower than those in the model control group( P < 0. 05). The liver index in the model control group was higher than that in the other 3 groups( P < 0. 01). In the model control group,the hepatic lobules and hepatic cords were disordered,and the hepatocytes were swollen and accompanied by necrosis and cytoplasm loose. However,in the WP low-dose and high-dose groups,liver lobules arranged neatly,liver cell swelling and cytoplasmic extent were significantly reduced compared with those in the model control group,liver cell morphology was uniform,and arranged in regular. The SOD level of liver tissue in the model control group was lower while the MDA level was higher than in the normal control group( P < 0. 01). WP low-dose group,WP high-dose group had higher SOD level but lower MDA level than the model control group( P < 0. 05). Conclusion WP has good protective effects on liver injury caused by CTX and its mechanism is probably related to the scavenging of free radical and increasing of cell anti-oxidative function.
引文
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[4]张长城,贾亮亮,许佳,等.五子衍宗汤对环磷酰胺致小鼠生精障碍保护作用的研究[J].中国中医基础医学杂志,2010,16(7):570-571.ZHANG C C,JIA L L,XU J,et al.Protective effect of Wuzi yanzong decoction on dyszoospermia induced by cycoxan in mice[J].Chinese Journal of Basic Medicine in Traditional Chinese Medicine,2010,16(7):570-571.
[5]王洪武,贾亮亮,徐媛青,等.五子衍宗汤对环磷酰胺致免疫低下小鼠的免疫调节作用[J].中国实验方剂学杂志,2011,17(4):144-146.DOI:10.3969/j.issn.1005-9903.2011.04.044.WANG H W,JIA L L,XU Y Q,et al.Immuno-regulation effects of Wuzi Yanzong decoction on immunosuppression mice[J].Chinese Journal of Experimental Traditional Medical Formula,2011,17(4):144-146.DOI:10.3969/j.issn.1005-9903.2011.04.044.
[6]欧琴,何坚.加味五子衍宗汤治疗脂肪肝82例[J].陕西中医,2003,24(7):587.DOI:10.3969/j.issn.1000-7369.2003.07.007.OU Q,HE J.Treatment of 82 cases of fatty liver with flavored Wuzi Yanzong decoction[J].Shaanxi Journal of Traditional Chinese Medicine,2003,24(7):587.DOI:10.3969/j.issn.1000-7369.2003.07.007.
[7]黄威峰,刘苗苗,袁丁,等.五子衍宗方对环磷酰胺致小鼠肝脏细胞DNA损伤的保护作用[J].中成药,2015,37(5):1093-1096.DOI:3969/j.ssn.1001-1528.2015.05.038.HUANG W F,LIU M M,YUAN D,et al.Protective effect of Wuzi Yanzong recipe on DNA damage induced by cyclophosphamide in liver cells of mice[J].Chinese Traditional Patent Medicine,2015,37(5):1093-1096.DOI:3969/j.ssn.1001-1528.2015.05.038.
[8]刘苗苗,袁丁,黄威峰,等.五子衍宗方对环磷酰胺致小鼠DNA损伤的影响[J].中国中医药信息杂志,2014,21(6):38-40.DOI:10.3969/j.issn.1005-5304.2014.06.014.LIU M M,YUAN D,HUANG W F,et al.Effect of Wuzi Yanzong Fang against cyclophosphamide induced DNA damage in mice[J].Chinese Journal of Information on TCM,2014,21(6):38-40.DOI:10.3969/j.issn.1005-5304.2014.06.014.
[9]黄秀曼,杜钢军,孙婷,等.过山蕨总黄酮对肝损伤的保护作用[J].中草药,2012,43(12):2458-2463.HUANG X M,DU G J,SUN T,et al.Protection of total flavonoids from Camptosorus sibiricus on hepatic injury[J].Chinese Traditional and Herbal Drugs,2012,43(12):2458-2463.
[10]王志旺,王瑞琼,郭玫,等.甘肃产藏药五脉绿绒蒿总黄酮对小鼠实验性肝损伤的保护作用[J].中国实验方剂学杂志,2013,19(2):206-209.DOI:10.13422/j.cnki.syfjx.2013.02.006.WANG Z W,WANG R Q,GUO M,et al.Study on liver protection of total flavones of meconopsis quintuplinervia from Gansu Province in mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2013,19(2):206-209.DOI:10.13422/j.cnki.syfjx.2013.02.006.
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