[1]徐艳敏,靳世英,吴洁.大蒜素对2型糖尿病大鼠肝脏病理学改变的影响[J].新乡医学院学报,2023,40(6):515-522.[doi:10.7683/xxyxyxb.2023.06.003]
　XU Yanmin,JIN Shiying,WU Jie.Effect of Allicin on the pathological changes of liver in rats with by type 2 diabetes mellitus[J].Journal of Xinxiang Medical University,2023,40(6):515-522.[doi:10.7683/xxyxyxb.2023.06.003]
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大蒜素对2型糖尿病大鼠肝脏病理学改变的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
40卷
期数:
2023年6
页码:
515-522
栏目:
基础研究
出版日期:
2023-06-05

文章信息/Info

Title:
Effect of Allicin on the pathological changes of liver in rats with by type 2 diabetes mellitus
作者:
徐艳敏; 靳世英; 吴洁
（邯郸市中心医院药学部，河北　邯郸　056000）
Author(s):
XU Yanmin; JIN Shiying; WU Jie
(Department of Pharmacy,Handan Central Hospital,Handan 056000,Hebei Province,China)
关键词:
大蒜素; 糖尿病; 肝脏; 病理学变化; 超微结构
Keywords:
Allicin; diabetes mellitus; liver; pathological change; ultrastructure
分类号:
R285.5
DOI:
10.7683/xxyxyxb.2023.06.003
文献标志码:
A
摘要:
目的　探讨大蒜素对2型糖尿病（T2DM）大鼠肝脏组织病理学改变的影响。方法　取55只大鼠给予高脂高糖饮食6周后，采用腹腔注射链尿佐菌素的方法制备T2DM模型；另取10只大鼠作为正常对照组，给予常规饲料喂养。取50只造模成功大鼠随机分为模型组、二甲双胍组、低剂量大蒜素组、中剂量大蒜素组和高剂量大蒜素组。二甲双胍组大鼠灌胃给予二甲双胍300 mg·kg-1，每日1次，共4周；低、中、高剂量大蒜素组大鼠分别灌胃给予大蒜素5、10、20 mg·kg-1，每日1次，共4周；正常对照组和模型组大鼠灌胃给予生理盐水（10 mL·kg-1），每日1次，共4周。干预4周后，经尾静脉采集各组大鼠空腹血1 mL，测定空腹血糖（FBG）水平;称量各组大鼠体质量并计算肝脏系数；经腹主动脉采血5 mL，应用全自动生物化学分析仪检测各组大鼠血清丙氨酸转氨酶 (ALT）、天冬氨酸转氨酶 (AST）、总胆红素（TBIL）水平；观察各组大鼠肝脏大体外观变化，苏木精-伊红染色观察各组大鼠肝脏组织病理学变化，并计算非酒精性肝脏损伤评分（NAS）；Masson染色法观察肝组织纤维化状况，计算胶原容积分数（CVF）；应用透射电子显微镜观察肝细胞超微结构变化。结果　模型组大鼠的FBG水平和肝脏系数显著高于正常对照组，体质量显著低于正常对照组（P<0.05）。二甲双胍组、中剂量大蒜素组、高剂量大蒜素组大鼠的FBG水平和肝脏系数显著低于模型组，体质量显著高于模型组（P<0.05）；低剂量大蒜素组与模型组大鼠的FBG水平、体质量及肝脏系数比较差异无统计学意义（P>0.05）。低剂量大蒜素组大鼠的FBG水平和肝脏系数显著高于二甲双胍组，体质量显著低于二甲双胍组（P<0.05）；中剂量大蒜素组大鼠的FBG水平显著高于二甲双胍组（P<0.05）；中剂量大蒜素组与二甲双胍组大鼠的体质量和肝脏系数比较差异无统计学意义（P>0.05）；高剂量大蒜素组与二甲双胍组大鼠的FBG水平比较差异无统计学意义（P>0.05）；高剂量大蒜素组大鼠的体质量显著高于二甲双胍组，肝脏系数显著低于二甲双胍组（P<0.05）。中剂量大蒜素组大鼠的FBG水平和肝脏系数显著低于低剂量大蒜素组（P<0.05）；中剂量大蒜素组与低剂量大蒜素组大鼠的体质量比较差异无统计学意义（P>0.05）。高剂量大蒜素组大鼠的FBG水平和肝脏系数显著低于低剂量大蒜素组，体质量显著高于低剂量大蒜素组（P<0.05）。高剂量大蒜素组大鼠的体质量显著高于中剂量大蒜素组（P<0.05）；高剂量大蒜素组与中剂量大蒜素组大鼠的FBG水平和肝脏系数比较差异无统计学意义（P>0.05）。模型组大鼠血清ALT、AST、TBIL水平显著高于正常对照组（P<0.05）。二甲双胍组、中剂量大蒜素组、高剂量大蒜素组大鼠血清ALT、AST、TBIL水平显著低于模型组（P<0.05），低剂量大蒜素组与模型组大鼠血清ALT、AST、TBIL水平比较差异无统计学意义（P>0.05）。低剂量大蒜素组大鼠血清ALT、AST、TBIL水平显著高于二甲双胍组（P<0.05）,中剂量大蒜素组与二甲双胍组大鼠血清ALT、AST、TBIL水平比较差异无统计学意义（P>0.05），高剂量大蒜素组大鼠血清ALT、AST、TBIL水平显著低于二甲双胍组（P<0.05）。中剂量大蒜素组和高剂量大蒜素组大鼠血清ALT、AST、TBIL水平显著低于低剂量大蒜素组（P<0.05），高剂量大蒜素组大鼠血清ALT、AST、TBIL水平显著低于中剂量大蒜素组（P<0.05）。正常对照组大鼠肝脏外观呈红褐色、色泽鲜亮，包膜光滑，边缘锐利，质软且有弹性；肝小叶结构完整清晰，肝细胞形态正常、排列整齐；肝细胞核仁完整、核膜清晰，线粒体和内质网形态结构未见异常。模型组大鼠肝脏外观呈深褐色、无光泽，肝包膜呈颗粒状，可见散在结节，边缘粗糙，质硬无弹性；肝小叶结构模糊、假性肝小叶形成，肝细胞肿胀呈空泡样脂肪变性，中央静脉周围及汇管区胶原纤维明显增粗并形成纤维隔；肝细胞可见核膜破裂、核仁溶解，线粒体肿大、破裂，内质网扩张，细胞质中可见大量脂滴，Disse间隙增大并可见胶原纤维增生。与模型组相比，低、中、高剂量大蒜素组和二甲双胍组大鼠肝脏大体外观、病理学改变及肝细胞超微结构呈不同程度改善。模型组大鼠NAS评分和CVF显著高于正常对照组（P<0.05）。二甲双胍组、中剂量大蒜素组、高剂量大蒜素组大鼠NAS评分和CVF显著低于模型组（P<0.05）；低剂量大蒜素组与模型组大鼠NAS评分和CVF比较差异无统计学意义（P>0.05）。低剂量大蒜素组大鼠NAS评分和CVF显著高于二甲双胍组（P<0.05）；中剂量大蒜素组、高剂量大蒜素组大鼠NAS评分和CVF显著低于二甲双胍组（P<0.05）。中剂量大蒜素组、高剂量大蒜素组大鼠NAS评分和CVF显著低于低剂量大蒜素组（P<0.05）。高剂量大蒜素组大鼠NAS评分和CVF显著低于中剂量大蒜素组（P<0.05）。结论　大蒜素对T2DM大鼠肝脏病理学改变及超微结构病变具有改善作用。
Abstract:
Objective　To investigate the effect of Allicin on the pathological changes of liver in rats with type 2 diabetes mellitus (T2DM).Methods　Fifty-five rats were taken and fed with high-fat and high-sugar diet for 6 weeks,then the rats were intraperitoneally injected with streptozotocin to prepare T2DM models.Other 10 rats were taken as the normal control group and fed with convertional forage.Fifty T2DM rat were taken and randomly divided into model group,metformin group,low-dose Allicin group,medium-dose Allicin group and high-dose Allicin group.The rats in metformin group were given metformin 300 mg·kg-1 by intragastric administration,once a day for 4 weeks;the rats in the low-,medium-,high-dose Allicin groups were given Allicin 5,10,20 mg·kg-1 by intragastric administration,respectively,once a day for 4 weeks;the rats in normal control group and model group were given normal saline(10 mL·kg-1) by intragastric administration,once a day for 4 weeks.After 4 weeks of intervention,1 mL fasting blood was collected from rats in each group through the tail vein to determine the level of?FBG;the body mass of rats in each group was measured and the liver coefficient was calculated;5 mL blood was collected through abdominal aorta,and the levels of?ALT, AST and?TBIL in serum of rats in each group were detected by automatic biochemical analyzer.The liver was collected to observe the changes of gross appearance of rats in each group.The liver histopathological changes of rats in each group were observed by hematoxylin-eosin staining,and the nonalcoholic fatty liver disease activity score (NAS) was calculated.The liver tissue fibrosis of rats in each group was observed by Masson staining,and the CVF was calculated.The ultrastructure of liver cells was observed by transmission electron microscope.Results　The FBG level and liver coefficient of rats in the model group were significantly higher than those in the normal control group,the body mass was significantly lower than that in the normal control group (P<0.05).The FBG level and liver coefficient of rats in the metformin group,medium-dose Allicin group and high-dose Allicin group were significantly lower than those in the model group,while the body mass was significantly higher than that in the model group (P<0.05).The FBG level and liver coefficient of rats in the low-dose Allicin group were significantly higher than those in the metformin group,the body mass was significantly lower than that in the metformin group (P<0.05).There was no significant difference in FBG level between the high-dose Allicin group and the metformin group (P>0.05);the body mass of rats in the high-dose Allicin group was significantly higher than that in the metformin group,and the liver coefficient was significantly lower than that in the metformin group (P<0.05).The FBG level and liver coefficient of rats in the medium-dose Allicin group were significantly lower than those in the low-dose Allicin group (P<0.05);there was no significant difference in body mass between the medium-dose Allicin group and the low-dose Allicin group (P>0.05).The FBG level and liver coefficient of rats in the high-dose Allicin group were significantly lower than those in the low-dose Allicin group,and the body mass was significantly higher than that in the low-dose Allicin group (P<0.05).The serum levels of ALT,AST and TBIL of rats in the model group were significantly higher than those in the normal control group (P<0.05).The serum levels of ALT,AST and TBIL of rats in the metformin group,medium-dose Allicin group and high-dose Allicin group were significantly lower than those in the model group (P<0.05);there was no significant difference in the serum ALT,AST and TBIL levels of rats between the low-dose Allicin group and the model group (P>0.05).The serum levels of ALT,AST and TBIL of rats in the low-dose Allicin group were significantly higher than those in the metformin group (P<0.05);there was no significant difference in serum ALT,AST and TBIL levels of rats between the medium-dose Allicin group and the metformin group (P>0.05);the serum ALT,AST and TBIL levels of rats in the high-dose Allicin group were significantly lower than those in the metformin group (P<0.05).The serum ALT,AST and TBIL levels of rats in the medium-dose Allicin group and high-dose Allicin group were significantly lower than those in the low-dose Allicin group (P<0.05);the serum ALT,AST and TBIL levels of rats in the high-dose Allicin group were significantly lower than those in the medium-dose Allicin group (P<0.05).The liver of rats in the normal control group had a reddish brown appearance,bright color,smooth capsule,sharp edges,soft and elastic texture;the structure of liver lobules were complete and clear,and the morphology of liver cells was normal and neatly arranged;the nucleolus of hepatocytes was complete,the nuclear membrane was clear,and the morphological structure of mitochondria and endoplasmic reticulum was normal.The appearance of the liver of rats in the model group rats was dark brown and matte,with a granular liver capsule and scattered nodules,rough edges,and hard and inelastic texture;the structure of the hepatic lobule was blurred,the pseudo hepatic lobule was formed,the hepatocytes were swollen with vacuolar steatosis,and the collagen fibers around the central vein and the portal area were significantly thickened and fibrous septa were formed;the nuclear membrane of hepatocytes was broken,nucleolus was dissolved,mitochondria was swollen and broken,endoplasmic reticulum was expanded,a large number of lipid droplets could be seen in the cytoplasm,and the Disse gap was enlarged and collagen fiber proliferation could be seen.Compared with the model group,the appearance,histopathology changes of the liver and the ultrastructure of liver cells of rats in the low-,medium-,and high-dose Allicin groups and metformin group showed varying degrees of improvement.The NAS score and CVF of rats in the model group were significantly higher than those in the normal control group (P<0.05).The NAS score and CVF of rats in the metformin group,medium-dose Allicin group,and high-dose Allicin group were significantly lower than those in the model group (P<0.05).The NAS score and CVF of rats in the low-dose Allicin group were significantly higher than those in the metformin-group (P<0.05);the NAS score and CVF of rats in the medium-dose Allicin group and high-dose Allicin group were significantly lower than those in the metformin group (P<0.05).The NAS score and CVF of rats in the medium-dose Allicin group and high-dose Allicin group were significantly lower than those in the low-dose Allicin group (P<0.05).The NAS score and CVF of rats in the high-dose Allicin group were significantly lower than those in the medium-dose Allicin group (P<0.05).Conclusion　Allicin has improving effect on pathological changes and ultrastructural changes of liver in T2DM rats.

参考文献/References:

［1］　CHO N H,SHAW J E,KARURANGA S,et al.IDF diabetes atlas：global estimates of diabetes prevalence for 2017 and projections for 2045［J］.Diabetes Res Clin Pract,2018,138：271-281.
［2］　RHEE E J.Nonalcoholic fatty liver disease and diabetes：an epidemiological perspective［J］.Endocrinol Metab (Seoul)，2019,34(3)：226-233.
［3］　MOUSA A M,SOLIMAN K E A,ALHUMAYDHI F A,et al.Could allicin alleviate trastuzumab-induced cardiotoxicity in a rat model through antioxidant,anti-inflammatory,and antihyperlipidemic properties［J］.Life Sci,2022,302(5)：120656.
［4］　韩淑琴,刘润,刘俊霞,等.二甲双胍对2型糖尿病合并非酒精性脂肪性肝病患者肝脏炎症、肝纤维化和胰岛素抵抗的影响［J］.河北医药,2018,40(12)：1769-1773.
HAN S Q,LIU R,LIU J X,et al.Effects of metformin on hepatic inflammation,liver fibrosis and insulin resistance in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease［J］.Hebei Med J,2018,40(12)：1769-1773.
［5］　LI W,HUANG R,GONG X,et al.Allicin attenuated hepatic ischemia/reperfusion injury in mice by regulating PPARγ-IRAK-M-TLR4 signal pathway［J］.Food Funct,2022,13(13)：7361-7376.
［6］　PANYOD S,WU W K,HO C T,et al.Diet supplementation with Allicin protects against alcoholic fatty liver disease in mice by improving anti-inflammation and antioxidative functions［J］.J Agric Food Chem,2016,64(38)：7104-7113.
［7］　高敏,彭玥,杨明施,等.大蒜素对脓毒症小鼠急性肝损伤的作用［J］.中国临床药理学杂志,2019,35(24)：3213-3216.
GAO M,PENG Y,YANG M S,et al.Effect of allicin on acute liver injury in sepsis mice［J］.Chin J Clin Pharmacol,2019,35(24)：3213-3216.
［8］　ZHU Y,SU Y,ZHANG J,et al.Astragaloside IV alleviates liver injury in type 2 diabetes due to promotion of AMPK/mTOR mediated autophagy［J］.Mol Med Rep,2021,23(6)：437.
［9］　徐静,李楠,王俊红,等.二甲双胍对2型糖尿病合并非酒精性脂肪肝大鼠肝脏SIRT1和UCP2表达的影响［J］.中南大学学报(医学版),2013,38(9)：882-887.
XU J,LI N,WANG J H,et al.Effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus and nonalcoholic fatty liver［J］.J Central South Univ (Med Sci)，2013,38(9)：882-887.
［10］　张雪丹,陈振宙.大蒜素对链脲佐菌素所致糖尿病大鼠胰岛素抵抗及脂肪因子的影响［J］.西部中医药,2019,32(1)：23-26.
ZHANG X D,CHEN Z Z.Effects of Allitridi on insulin resistance and adipokines of the rats with streptozotocin-induced diabetes mellitus［J］.West J Tradit Chin Med,2019,32(1)：23-26.
［11］　KLEINER D E,BRUNT E M,VAN N M,et al.Design and validation of a histological scoring system for nonalcoholic fatty liver disease［J］.Hepatology,2005,41(6)：1313-1321.
［12］　FUJII H,KAWADA N,JAPAN STUDY GROUP OF NAFLD JSG-NAFLD.The role of insulin resistance and diabetes in nonalcoholic fatty liver disease［J］.Int J Mol Sci,2020,21(11)：3863-3672.
［13］　RADAKOVIC D,OPACIC D,BRGERMANN J,et al.Model for end-stage liver disease predicts mortality after pericardiectomy for constrictive pericarditis［J］.Interact Cardiovasc Thorac Surg,2018,27(6)：813-818.
［14］　吴进,王子龙,张忠勇,等.从郁、瘀、痰、浊论糖尿病微血管病变中医病因病机［J］.中医药临床杂志,2019,31(11)：1997-1999.
WU J,WANG Z L,ZHANG Z Y,et al.Discussion on the etiology and pathogenesis of diabetic microangiopathy in TCM from depression-stasis- phlegm-turbidity［J］.Clin J Tradit Chin Med,2019,31(11)：1997-1999.
［15］　彭思涵,谢子妍,谢春光,等.谢春光教授以气阴两虚为糖尿病核心病机的学术思想探析［J］.中华中医药学刊,2020,38(4)：83-85.
PENG S H,XIE Z Y,XIE C G,et al.Introduction of Xie Chunguang′s academic thoughts of considering qi and yin deficiency as the core pathogenesis of diabetes［J］.Chin Arch Tradit Chin Med,2020,38(4)：83-85.
［16］　GOORDEN S M,BUFFART T E,BAKKER A,et al.Liver disorders in adults：ALT and AST［J］.Ned Tijdschr Geneeskd,2013,157(43)：A6443.
［17］　XIONG X,REN Y,CUI Y,et al.Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation［J］.Biomed Pharmacother,2017,96(4)：1292-1298.
［18］　吴堃,蒋青松,任凯强,等.苯扎贝特减轻小鼠糖尿病肝损伤［J］.中国病理生理杂志,2020,36(3)：519-524.
WU K,JIANG Q S,REN K Q,et al.Activation of PPARs is involved in effect of bezafibrate on diabetic hepa-topathy in mice［J］.Chin J Pathophysiol,2020,36(3)：519-524.
［19］　ZHONG Y,LI Z,JIN R,et al.Diosgenin ameliorated type II diabetes-associated nonalcoholic fatty liver disease through inhibiting de novo lipogenesis and improving fatty acid oxidation and mitochondrial function in rats［J］.Nutrients,2022,14(23)：4994.
［20］　贾春新,张红利,李海鸥,等.参芍口服液对2型糖尿病大鼠肝脏超微结构及氧化应激的影响［J］.华北理工大学学报(医学版),2017,19(2)：131-136.
JIA C X,ZHANG H L,LI H O,et al.Effects of Shenshao oral liquid on liver ultrastructure and oxidative stress in type 2 diabetic rats［J］.J Nor Chin Univ Sci Tech (Med Sci)，2017,19(2)：131-136.
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[1]马晓军,霍慧春,刘娟,等.针灸联合中药对糖尿病大鼠血脂及血糖的调节作用[J].新乡医学院学报,,():000.
[2]郭永年.糖尿病氯磺丙脲酒精潮红试验[J].新乡医学院学报,1986,3(02):064.
[3]翁孝刚,郭永年,王宪波,等.复方中药渴乐饮对实验大鼠体重及血糖的影响 [J].新乡医学院学报,1994,11(02):107.
[4]郭永年,李灵敏,王伟,等.新光碘蛋的研制及其对糖尿病患者的保健作用 [J].新乡医学院学报,1994,11(04):339.
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[6]王宪波,翁孝刚,王伟,等.复方中药渴乐饮对实验大鼠的抗氧化抗疲劳作用[J].新乡医学院学报,1994,11(04):354.
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[8]王宪波,翁孝钢,郭永年,等.复方中药渴乐对实验糖尿病大鼠血脂的影响[J].新乡医学院学报,1995,12(01):018.
[9]王卫民,张清贵,王昕红,等.尿C—肽与Ⅱ型糖尿病患者的β细胞功能[J].新乡医学院学报,1996,13(01):044.
[10]索新华,陈志刚,郭永年,等.糖尿病性水疱病及其感染的临床治疗[J].新乡医学院学报,1997,14(01):057.

更新日期/Last Update: 2023-06-05