藏红花素对糖尿病大鼠胰腺组织保护作用的研究
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摘要
目的研究藏红花素(crocin)对2型糖尿病大鼠胰腺组织并发症损伤的保护作用并初探其机制。方法 120只实验用SD大鼠经过体重分层后随机分为正常组、模型对照组、藏红花素25、50、100mg/(kg·d)组和二甲双胍25mg/(kg·d)组,灌胃给药,疗程12周;采用链脲佐菌素(STZ)连续3天腹腔注射30mg/(kg·d)的方法制备实验性2型糖尿病大鼠模型。测定各组大鼠空腹血糖(FBG)、空腹胰岛素(FINS)和糖化血红蛋白(GHb),计算胰岛素抵抗指数(ISI)和敏感指数(HOMA-IR),采用HE染色对胰岛组织进行病理学检查,TUNEL法观察胰岛细胞凋亡状况,测定胰腺组织中抗氧化酶活性和丙二醛(MDA)含量。结果经藏红花素50～100mg/(kg·d)治疗12周,糖尿病大鼠FBG显著降低、FINS显著升高、GHb显著降低、ISI和HOMA-IR显著降低,差异均有统计学意义(P<0.05);胰岛组织病变明显改善,胰岛组织细胞凋亡数量明显减少,凋亡指数(apoptosis index,AI)显著降低(P<0.01);胰腺组织抗氧化酶[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)]活性显著升高且MDA含量显著降低(P<0.05)。结论藏红花素对2型糖尿病大鼠胰腺组织损伤具有一定的保护作用,其机制可能与抑制氧化应激损伤有关。
Objective To investigate the protective effects of crocin on pancreatic tissue injury in type 2 diabetic rats and its mechanism. Methods Totally 120 SD rats were randomized according to body weight divided into normal control group, model group, crocin [25, 50, 100 mg/(kg·d)] groups and metformin hydrochloride 25 mg/(kg·d) group. The drugs were given by gastric administration for 12 weeks. The diabetic rat models were made by intraperitoneal injecting STZ [30 mg/(kg·d)] for 3 days continuously. The general condition of the rats in every group were observed. The FBG, FINS, GHb were detected. The ISI and HOMA-IR were calculated. HE staining was used for pathological examination of islet tissues and TUNEL was used to observe the apoptosis of islet cells. The antioxidant enzyme activity and malondialdehyde(MDA) content in pancreatic tissues were detected. Results After treatment with crocin 50～100 mg/(kg·d) for 12 weeks, the FBG decreased significantly, FINS increased significantly, GHb decreased significantly, ISI and HOMA-IR significantly decreased. All of the differences above were statistically significant(P<0.05). The islet tissue lesions significantly improved, islet cell apoptosis was significantly reduced, apoptotic index was significantly reduced(P<0.01). The antioxidant enzymes(SOD, CAT) activity increased significantly and MDA content decreased significantly in pancreatic tissue(P<0.05). ConclusionCrocin has a protective effect on diabetic pancreatic tissue injury, and its mechanism may be related to the inhibition of oxidative stress injury.
Objective To investigate the protective effects of crocin on pancreatic tissue injury in type 2 diabetic rats and its mechanism. Methods Totally 120 SD rats were randomized according to body weight divided into normal control group, model group, crocin [25, 50, 100 mg/(kg·d)] groups and metformin hydrochloride 25 mg/(kg·d) group. The drugs were given by gastric administration for 12 weeks. The diabetic rat models were made by intraperitoneal injecting STZ [30 mg/(kg·d)] for 3 days continuously. The general condition of the rats in every group were observed. The FBG, FINS, GHb were detected. The ISI and HOMA-IR were calculated. HE staining was used for pathological examination of islet tissues and TUNEL was used to observe the apoptosis of islet cells. The antioxidant enzyme activity and malondialdehyde(MDA) content in pancreatic tissues were detected. Results After treatment with crocin 50～100 mg/(kg·d) for 12 weeks, the FBG decreased significantly, FINS increased significantly, GHb decreased significantly, ISI and HOMA-IR significantly decreased. All of the differences above were statistically significant(P<0.05). The islet tissue lesions significantly improved, islet cell apoptosis was significantly reduced, apoptotic index was significantly reduced(P<0.01). The antioxidant enzymes(SOD, CAT) activity increased significantly and MDA content decreased significantly in pancreatic tissue(P<0.05). ConclusionCrocin has a protective effect on diabetic pancreatic tissue injury, and its mechanism may be related to the inhibition of oxidative stress injury.
引文
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2 Elsherbiny NM,Salama MF,Said E,et al.Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways[J].Chem Biol Interact,2016,247:39-48
3 霍军丽,甄海宁,刘卫平,等.藏红花素对小鼠创伤性脑损伤保护作用的研究[J].现代生物医学进展,2013,13(10):1892-1894
4 吕明锐,王倩然,杨升东,等.藏红花及其组分抑制炎症因子表达的研究进展[J].重庆医学,2017,46(13):1850-1853
5 李赛,杨慧科,丁选胜.藏红花素对糖尿病大鼠胸主动脉环舒缩功能的影响[J].药学与临床研究,2017,25(3):183-186
6 郭斌,钦华,王莉,等.藏红花素对糖基化终产物诱导视网膜微血管内皮细胞凋亡的影响[J].医学研究生学报,2012,25(11):1141-1145
7 王素莲,黄伟,熊玉卿,等.藏红花降血脂作用的研究进展[J].中国临床药理学杂志,2015,31(12):1218-1220
8 Li GW,Pan XR,Stephen L,et al.A new insulin-sensitivity index for the population-based study [J].Chin J Intern Med,1993,32(10):656-660
9 Hanley AJ,Williams K,Gonzalez C,et al.Prediction of type 2 diabetes using simple measures of insulin resistance:combined results from the san antonio heart study,the mexico city diabetes study,and the insulin resistance atherosclerosis study[J].Diabetes,2003,52:463-469
10 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版) [J].中华糖尿病杂志,2018,10(1):4-67
11 石亚静,张欢,李云翠,等.熊果酸对糖尿病大鼠一般表征和糖脂代谢的影响[J].中国执业药师,2016,13(7):25-30
12 柳蕾,匡少金,刘财德,等.火绒草对2型糖尿病大鼠糖脂代谢的影响[J].中国现代医药杂志,2014,16(6):11-13
13 彭韦霞,贺佩祥,刘丽君,等.新诊断非酮症糖尿病患者胰岛相关自身抗体与甲状腺抗体的相关性研究[J].中国糖尿病杂志,2018,26(2):128-132
14 桂书彦,韩瑾,叶强,等.TCF7L2在2型糖尿病大鼠胰岛中的表达及影响[J].医学研究杂志,2015,44(2):133-137
15 陆春丽,胡东辉,褚加成,等.利拉鲁肽对糖尿病前期小鼠胰岛功能及胰岛微血管内皮细胞作用的研究[J].中国糖尿病杂志,2018,26(5):412-416
16 张慧,王新玲,张宏武,等.维吾尔族、汉族新诊断2型糖尿病患者胰岛素分泌与胰岛素抵抗[J].医学研究杂志,2018,47(3):57-61
17 门秀丽,赵霞,赵利军,等.牛磺酸对2型糖尿病大鼠胰腺线粒体氧化应激的影响[J].中国药理学通报,2009,25(10):1373-1375
18 Yildirim T,Alp R.The role of oxidative stress in the relation between fibromyalgia and obstructive sleep apnea syndrome[J].Eur Rev Med Pharmacol Sci,2017,21(1):20-29
19 Lu X,Wang C,Liu B.The role of Cu/Zn-SOD and Mn-SOD in the immune response to oxidative stress and pathogen challenge in the clam meretrix[J].Fish Shellfish Immunol,2015,42(1):58-65
20 Sravanthi KN,Rao NR.Cerebroprotective activity of pentapetes phoenicea on global cerebral ischemia in rats[J].Indian J Pharmacol,2016,48(6):694-700
21 蔡旗旗,张盛,应盼,等.依达拉奉对百草枯致大鼠肾脏氧化应激因子及HO-1表达的影响[J].医学研究杂志,2017,46(1):101-104
22 Kaminski K,Bonda T,Wojtkowska I,et al.Oxidative stress and antioxidative defense parameters early after reperfusion therapy for acute myocardial infarction [J].Acute Card Care,2008,10(2):121-126
23 彭朝胜,曹悦鞍,夏菁,等.隐匿性高血压患者血清SOD、MDA与NO的水平变化[J].医学研究杂志,2014,43(11):121-124
2 Elsherbiny NM,Salama MF,Said E,et al.Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways[J].Chem Biol Interact,2016,247:39-48
3 霍军丽,甄海宁,刘卫平,等.藏红花素对小鼠创伤性脑损伤保护作用的研究[J].现代生物医学进展,2013,13(10):1892-1894
4 吕明锐,王倩然,杨升东,等.藏红花及其组分抑制炎症因子表达的研究进展[J].重庆医学,2017,46(13):1850-1853
5 李赛,杨慧科,丁选胜.藏红花素对糖尿病大鼠胸主动脉环舒缩功能的影响[J].药学与临床研究,2017,25(3):183-186
6 郭斌,钦华,王莉,等.藏红花素对糖基化终产物诱导视网膜微血管内皮细胞凋亡的影响[J].医学研究生学报,2012,25(11):1141-1145
7 王素莲,黄伟,熊玉卿,等.藏红花降血脂作用的研究进展[J].中国临床药理学杂志,2015,31(12):1218-1220
8 Li GW,Pan XR,Stephen L,et al.A new insulin-sensitivity index for the population-based study [J].Chin J Intern Med,1993,32(10):656-660
9 Hanley AJ,Williams K,Gonzalez C,et al.Prediction of type 2 diabetes using simple measures of insulin resistance:combined results from the san antonio heart study,the mexico city diabetes study,and the insulin resistance atherosclerosis study[J].Diabetes,2003,52:463-469
10 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版) [J].中华糖尿病杂志,2018,10(1):4-67
11 石亚静,张欢,李云翠,等.熊果酸对糖尿病大鼠一般表征和糖脂代谢的影响[J].中国执业药师,2016,13(7):25-30
12 柳蕾,匡少金,刘财德,等.火绒草对2型糖尿病大鼠糖脂代谢的影响[J].中国现代医药杂志,2014,16(6):11-13
13 彭韦霞,贺佩祥,刘丽君,等.新诊断非酮症糖尿病患者胰岛相关自身抗体与甲状腺抗体的相关性研究[J].中国糖尿病杂志,2018,26(2):128-132
14 桂书彦,韩瑾,叶强,等.TCF7L2在2型糖尿病大鼠胰岛中的表达及影响[J].医学研究杂志,2015,44(2):133-137
15 陆春丽,胡东辉,褚加成,等.利拉鲁肽对糖尿病前期小鼠胰岛功能及胰岛微血管内皮细胞作用的研究[J].中国糖尿病杂志,2018,26(5):412-416
16 张慧,王新玲,张宏武,等.维吾尔族、汉族新诊断2型糖尿病患者胰岛素分泌与胰岛素抵抗[J].医学研究杂志,2018,47(3):57-61
17 门秀丽,赵霞,赵利军,等.牛磺酸对2型糖尿病大鼠胰腺线粒体氧化应激的影响[J].中国药理学通报,2009,25(10):1373-1375
18 Yildirim T,Alp R.The role of oxidative stress in the relation between fibromyalgia and obstructive sleep apnea syndrome[J].Eur Rev Med Pharmacol Sci,2017,21(1):20-29
19 Lu X,Wang C,Liu B.The role of Cu/Zn-SOD and Mn-SOD in the immune response to oxidative stress and pathogen challenge in the clam meretrix[J].Fish Shellfish Immunol,2015,42(1):58-65
20 Sravanthi KN,Rao NR.Cerebroprotective activity of pentapetes phoenicea on global cerebral ischemia in rats[J].Indian J Pharmacol,2016,48(6):694-700
21 蔡旗旗,张盛,应盼,等.依达拉奉对百草枯致大鼠肾脏氧化应激因子及HO-1表达的影响[J].医学研究杂志,2017,46(1):101-104
22 Kaminski K,Bonda T,Wojtkowska I,et al.Oxidative stress and antioxidative defense parameters early after reperfusion therapy for acute myocardial infarction [J].Acute Card Care,2008,10(2):121-126
23 彭朝胜,曹悦鞍,夏菁,等.隐匿性高血压患者血清SOD、MDA与NO的水平变化[J].医学研究杂志,2014,43(11):121-124