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  本文選題：燈盞花素　切入點(diǎn)：2型糖尿病　出處：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：[目的]①觀察2型糖尿病合并心肌缺血大鼠發(fā)生胰島素抵抗時相關(guān)生化指標(biāo)空腹血糖(FBG)、甘油三酯(TG)、總膽固醇(TC)、游離脂肪酸(FFA)、空腹胰島素(FINS)、胰島素敏感指數(shù)(HOMA-IR)、心電圖、血流動力學(xué)指標(biāo)變化以及心臟、胰腺組織形態(tài)學(xué)的變化；②觀察燈盞花素干預(yù)后相關(guān)指標(biāo)的變化,探討其對模型防治作用可能的機(jī)制。 [方法]SD大鼠60只普通飼料適應(yīng)性喂養(yǎng)7天,均為雄性健康清潔級。禁食12h測空腹血糖,選擇血糖值正常的大鼠56只,隨機(jī)挑選12只作為正常對照組用普通飼料喂養(yǎng),其余44只用高脂高糖飼料喂養(yǎng)。4周后,一次性給予高脂高糖組大鼠左下腹注射小劑量鏈脲佐菌素(STZ)40mg·kg-1(配置用pH=4.4,0.lmol·L-1檸檬酸-檸檬酸鈉緩沖液)。給藥7天后,斷尾采血測空腹血糖值16.7mmol·L-1提示2型糖尿病造模成功。36只成模大鼠,隨機(jī)分為模型組、燈盞花素低劑量組、燈盞花素高劑量組(n=12)。成模后次日,低劑量組給予燈盞花素注射液100mg· kg-1· d-1,高劑量組給予燈盞花素注射液200mg· kg-1· d-1,給藥方式腹腔注射,連續(xù)給藥14天,正常組和模型組大鼠同時腹腔注射等體積的生理鹽水。實(shí)驗(yàn)給藥期間,除正常對照組外,其余各組繼續(xù)喂高脂高糖飼料,并每天稱量體重。給藥結(jié)束后次日,大鼠禁食12h,斷尾測空腹血糖值。各組大鼠腹腔注射10%水合氯醛麻醉,四肢皮下連接Ⅱ?qū)?lián)測體表心電圖。分離氣管并插管,經(jīng)右頸總動脈插管入左心室,用BL-420F生物機(jī)能實(shí)驗(yàn)系統(tǒng)記錄血流動力學(xué)指標(biāo)；按6mg·kg-1腹腔注射異丙腎上腺素(ISO),記錄給藥后每隔5分鐘心電圖的變化,觀察心電圖ST段偏移和T波的改變情況。腹主動脈取血,比色法測TC、 TG、FFA, ELISA法檢測血清FINS,計算穩(wěn)態(tài)模式胰島素抵抗指數(shù)(HOMA-IR)=FPG (mmol·L-1)×FINS (mmol·L-1)/22.5。胰腺、心臟取材做HE染色。 [結(jié)果] 1、心電圖與正常對照組相比,各時間點(diǎn)模型組大鼠ST偏移明顯(P0.05),T波抬高顯著(P0.05)；與模型組相比,燈盞花素高、低劑量組能明顯改善ST偏移和T波抬高(P0.05),高劑量組較低劑量組改善ST偏移更為明顯(P0.05),T波抬高不顯著(P0.05)。 2、血清檢測與正常對照組相比,模型組大鼠FBG、FINS、TG、TC、FFA、 HOMA-IR明顯升高(P0.05),體重明顯下降(P0.05)；與模型組相比,燈盞花素高、低劑量組能使FBG、FINS、TG、TC、FFA、HOMA-IR降低(P0.05),體重增加(P0.05)；而高劑量組較低劑量組FBG、FINS、TG、TC、FFA、 HOMA-IR明顯降低(P0.05),體重明顯增加(P0.05)。 3、血流動力學(xué)指標(biāo)與正常對照組相比,各時間點(diǎn)模型組大鼠LVSP、±dp/dtmax明顯下降,LVEDP明顯升高(P0.05)。與模型組相比,燈盞花素高、低劑量組能使LVSP、±dp/dtmax升高,LVEDP下降(P0.05)。而高劑量組較低劑量組LVSP、±dp/dtmax明顯升高,LVEDP明顯下降(P0.05)。 4、HE染色對照①胰腺組織病理變化：正常組大鼠鏡下胰島數(shù)目豐富,呈圓形或橢圓形,體積較大,邊界清,胰島細(xì)胞細(xì)胞質(zhì)豐富,細(xì)胞核位置居中間；模型組大鼠胰島萎縮,邊界不規(guī)則,胰島細(xì)胞體積增大,形態(tài)異常,細(xì)胞核分布偏心；高、低劑量組較模型組病變輕微,胰島數(shù)目增多,胰島細(xì)胞形態(tài)較規(guī)則,整齊排列,細(xì)胞質(zhì)增多,而高劑量組較低劑量組改善明顯。 ②心臟組織病理變化：正常組大鼠肌漿紅染,心肌纖維有序排列,細(xì)胞核位置居中,無炎細(xì)胞浸潤。模型組大鼠胞質(zhì)紅染,心肌纖維出現(xiàn)裂斷、排列雜亂無章,呈疏松水腫狀,細(xì)胞核偏心分布、形態(tài)異常,可見嗜酸變性。高、低劑量組較模型組病變較輕,有明顯改善,其中高劑量組改善尤為明顯,心肌纖維無斷裂,整齊排列,細(xì)胞核居中,輕微嗜酸變性。 [結(jié)論]①燈盞花素可以通過調(diào)節(jié)血脂紊亂、改善胰島素抵抗,保護(hù)2型糖尿病心肌缺血大鼠心臟功能。②燈盞花素對2型糖尿病大鼠并發(fā)癥引起的心臟、胰腺損傷具有保護(hù)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.

【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R285.5

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