灯盏花素对2型糖尿病合并心肌缺血大鼠胰岛素抵抗及心功能的影响

发布时间：2018-03-30 20:24

本文选题：灯盏花素　切入点：2型糖尿病　出处：《山西医科大学》2014年硕士论文

【摘要】：[目的]①观察2型糖尿病合并心肌缺血大鼠发生胰岛素抵抗时相关生化指标空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA)、空腹胰岛素(FINS)、胰岛素敏感指数(HOMA-IR)、心电图、血流动力学指标变化以及心脏、胰腺组织形态学的变化；②观察灯盏花素干预后相关指标的变化,探讨其对模型防治作用可能的机制。 [方法]SD大鼠60只普通饲料适应性喂养7天,均为雄性健康清洁级。禁食12h测空腹血糖,选择血糖值正常的大鼠56只,随机挑选12只作为正常对照组用普通饲料喂养,其余44只用高脂高糖饲料喂养。4周后,一次性给予高脂高糖组大鼠左下腹注射小剂量链脲佐菌素(STZ)40mg·kg-1(配置用pH=4.4,0.lmol·L-1柠檬酸-柠檬酸钠缓冲液)。给药7天后,断尾采血测空腹血糖值16.7mmol·L-1提示2型糖尿病造模成功。36只成模大鼠,随机分为模型组、灯盏花素低剂量组、灯盏花素高剂量组(n=12)。成模后次日,低剂量组给予灯盏花素注射液100mg· kg-1· d-1,高剂量组给予灯盏花素注射液200mg· kg-1· d-1,给药方式腹腔注射,连续给药14天,正常组和模型组大鼠同时腹腔注射等体积的生理盐水。实验给药期间,除正常对照组外,其余各组继续喂高脂高糖饲料,并每天称量体重。给药结束后次日,大鼠禁食12h,断尾测空腹血糖值。各组大鼠腹腔注射10%水合氯醛麻醉,四肢皮下连接Ⅱ导联测体表心电图。分离气管并插管,经右颈总动脉插管入左心室,用BL-420F生物机能实验系统记录血流动力学指标；按6mg·kg-1腹腔注射异丙肾上腺素(ISO),记录给药后每隔5分钟心电图的变化,观察心电图ST段偏移和T波的改变情况。腹主动脉取血,比色法测TC、 TG、FFA, ELISA法检测血清FINS,计算稳态模式胰岛素抵抗指数(HOMA-IR)=FPG (mmol·L-1)×FINS (mmol·L-1)/22.5。胰腺、心脏取材做HE染色。 [结果] 1、心电图与正常对照组相比,各时间点模型组大鼠ST偏移明显(P0.05),T波抬高显著(P0.05)；与模型组相比,灯盏花素高、低剂量组能明显改善ST偏移和T波抬高(P0.05),高剂量组较低剂量组改善ST偏移更为明显(P0.05),T波抬高不显著(P0.05)。 2、血清检测与正常对照组相比,模型组大鼠FBG、FINS、TG、TC、FFA、 HOMA-IR明显升高(P0.05),体重明显下降(P0.05)；与模型组相比,灯盏花素高、低剂量组能使FBG、FINS、TG、TC、FFA、HOMA-IR降低(P0.05),体重增加(P0.05)；而高剂量组较低剂量组FBG、FINS、TG、TC、FFA、 HOMA-IR明显降低(P0.05),体重明显增加(P0.05)。 3、血流动力学指标与正常对照组相比,各时间点模型组大鼠LVSP、±dp/dtmax明显下降,LVEDP明显升高(P0.05)。与模型组相比,灯盏花素高、低剂量组能使LVSP、±dp/dtmax升高,LVEDP下降(P0.05)。而高剂量组较低剂量组LVSP、±dp/dtmax明显升高,LVEDP明显下降(P0.05)。 4、HE染色对照①胰腺组织病理变化：正常组大鼠镜下胰岛数目丰富,呈圆形或椭圆形,体积较大,边界清,胰岛细胞细胞质丰富,细胞核位置居中间；模型组大鼠胰岛萎缩,边界不规则,胰岛细胞体积增大,形态异常,细胞核分布偏心；高、低剂量组较模型组病变轻微,胰岛数目增多,胰岛细胞形态较规则,整齐排列,细胞质增多,而高剂量组较低剂量组改善明显。 ②心脏组织病理变化：正常组大鼠肌浆红染,心肌纤维有序排列,细胞核位置居中,无炎细胞浸润。模型组大鼠胞质红染,心肌纤维出现裂断、排列杂乱无章,呈疏松水肿状,细胞核偏心分布、形态异常,可见嗜酸变性。高、低剂量组较模型组病变较轻,有明显改善,其中高剂量组改善尤为明显,心肌纤维无断裂,整齐排列,细胞核居中,轻微嗜酸变性。 [结论]①灯盏花素可以通过调节血脂紊乱、改善胰岛素抵抗,保护2型糖尿病心肌缺血大鼠心脏功能。②灯盏花素对2型糖尿病大鼠并发症引起的心脏、胰腺损伤具有保护作用。
[Abstract]:[Objective] to observe the occurrence of insulin resistance in type 2 diabetes mellitus complicated with myocardial ischemia rats and related biochemical indexes of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), fasting insulin (FINS), insulin sensitivity index (HOMA-IR), electrocardiogram, hemodynamics and changes the heart, the morphological changes of pancreatic tissue; to observe changes of breviscapine dry prognosis, and explore the possible mechanism of the prevention and treatment of the model.
Methods 60]SD rats with normal diet fed for 7 days, were male healthy 12h. Fasting fasting blood glucose, blood glucose of normal select 56 rats, randomly selected 12 rats as normal control group fed with normal diet, the other 44 with high fat diet after.4 weeks, one-time grant high fat and high glucose group rats left lower abdominal injection of low dose streptozotocin (STZ) 40mg - kg-1 (pH=4.4,0.lmol - L-1 citric acid sodium citrate buffer configuration). After 7 days of treatment, tail were measured fasting blood glucose 16.7mmol L-1 suggest that type 2 diabetes rats.36 model rats were randomly divided into model group, low dose group of Erigeron breviscapine, high dose group (n=12). The next day after modeling, the low dose group treated with Breviscapine Injection 100mg - kg-1 - D-1, the high dose group was given Breviscapine Injection 200mg - kg-1 - D-1, administered by intraperitoneal injection, continuous 14 days after drug administration, intraperitoneal injection of saline volume and normal group and model group rats. The experimental period of medication except the normal control group, other groups were fed with high fat diet, and weighed every day for the next day. After the treatment, the rats were fasted for 12h, fasting blood sugar value. Tail the rats received intraperitoneal injection of 10% chloral hydrate anesthesia, limbs subcutaneous connection lead II electrocardiogram. And measuring trachea intubation, intubation via right carotid artery into the left ventricle, used to record the blood dynamics index BL-420F biological function experimental system; according to the 6mg kg-1 by intraperitoneal injection of isoproterenol (ISO), were recorded after administration every 5 minutes to observe the ECG, ECG ST segment deviation and T wave changes. Blood from the abdominal aorta, colorimetry for TC, TG, FFA, serum FINS ELISA, calculated homeostasis model of insulin resistance index (HOMA-IR) =FPG (mmol, L-1 * FINS (mm) Ol. L-1) /22.5. pancreas, heart sampling for HE staining.
[results]
1, were compared with the normal control group, the rats in the model group at each time point ST offset (P0.05), T wave was significantly elevated (P0.05); compared with the model group, breviscapine high, low dose group can significantly improve the ST offset and T wave elevation (P0.05), high dose group and low dose group improved the ST offset is more obvious (P0.05), T wave elevation was not significant (P0.05).
2 serum samples compared with normal control group, model group rats FBG, FINS, TG, TC, FFA, HOMA-IR increased significantly (P0.05), body weight decreased significantly (P0.05); compared with the model group, breviscapine high, low dose group can make FBG, FINS, TG, TC, FFA, HOMA-IR decreased (P0.05), weight gain (P0.05); high dose group and low dose group FBG, FINS, TG, TC, FFA, HOMA-IR were significantly lower (P0.05), the body weight increased significantly (P0.05).
3, hemodynamic parameters compared with normal control group, while LVSP + dp/dtmax rats in model group decreased significantly, LVEDP increased significantly (P0.05). Compared with the model group, breviscapine high, low dose group can make the LVSP + dp/dtmax increased, LVEDP decreased (P0.05) and high dose group. Low dose group LVSP + dp/dtmax was significantly increased, LVEDP decreased significantly (P0.05).
4, HE staining pathological changes of pancreatic tissue: in control rats in the normal group under microscope, the number of islets rich, round or oval, large size, clear boundary, islet cell cytoplasm rich, nucleus position in the middle; model group of rat islet atrophy, irregular borders, islet cell volume, abnormal morphology, nuclear distribution eccentric; high, low dose group compared with model group, mild disease, pancreatic islet cell number, morphology is regular, neatly arranged, cytoplasm increased, high dose group and low dose group improved significantly.
The pathological changes of heart tissue of normal rats muscle cytolymph, myocardial fibers arranged orderly, nucleus position, no inflammatory cell infiltration. The rats in the model group the cytoplasm stained red, myocardial fibers were broken, arranged out of order, is loose and edema like, eccentric nucleus distribution, morphological abnormalities, visible eosinophilic degeneration. High and low dose group compared with the pathological model group is light, have significantly improved in high dose group improved obviously, myocardial fibers arranged neatly, nucleus centered, slight eosinophilic degeneration.
[Conclusion] breviscapine can regulate the blood lipid disorder and improve insulin resistance, and protect the heart function of type 2 diabetic rats with myocardial ischemia. 2. Breviscapine has protective effect on the heart and pancreas injury caused by complications of type 2 diabetes rats.

【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R285.5

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