番茄红素对糖尿病大鼠肾脏炎症抑制作用的研究

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目的:研究番茄红素(Lycopene,LP)对糖尿病大鼠肾脏炎症的抑制作用。方法:通过高脂高糖饮食加腹腔注射链脲佐菌素的方法制备糖尿病大鼠模型,取80只模型随机分为糖尿病模型组,盐酸二甲双胍200mg/kg治疗组和番茄红素(5、10、20mg/kg)治疗组,并另取16只同龄大鼠设为正常对照组;各组大鼠每天灌胃给药治疗一次,疗程4周。治疗满疗程后,通过血糖仪测定各组大鼠空腹血糖水平,称量体重并计算肾脏指数;测量24h尿量及24h尿蛋白量(UPro),测定各组大鼠血清中血尿素氮(BUN)、肌酐(SCr)含量;测定各组大鼠血清中总胆固醇(TC)、甘油三酯(TG)含量;酶联免疫法测定各组大鼠血浆中血浆C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)、细胞间黏附分子-1(ICAM-1)水平;RT-PCR法测定各组大鼠肾脏组织中AKT、bax和bcl-2 mRNA表达,并计算bax/bcl-2比值;通过PAS染色观察肾脏组织病理形态学变化。结果:与糖尿病模型组相比,番茄红素10、20 mg/kg治疗组大鼠体重显著升高、肾脏指数显著降低,20 mg/kg治疗组空腹血糖水平显著降低;番茄红素10、20 mg/kg治疗组大鼠24h尿量显著减少且UPro显著降低,血清中BUN、SCr含量显著降低,TC、TG含量显著降低;番茄红素10、20 mg/kg治疗组大鼠血浆中CRP、TNF-α、IL-1β、IL-6、ICAM-1水平均显著降低;番茄红素10、20 mg/kg治疗组肾脏组织中bax mRNA表达显著降低和bcl-2mRNA表达显著升高,bax/bcl-2比值显著降低,其中20 mg/kg治疗组AKT mRNA表达显著升高;番茄红素治疗组肾小球及肾脏组织病变均明显改善,其中以20 mg/kg治疗组效果最为显著。结论:番茄红素能够剂量依赖性地降低血糖、改善血脂,降低炎性介质水平,降低细胞间黏附分子,改善肾脏组织病变,提示番茄红素对糖尿病大鼠肾脏组织炎症具有剂量依赖性的抑制作用。 Objective: To study the inhibitory effect of Lycopene (LP) on renal inflammation in diabetic rats. Methods: A diabetic rat model was induced by intraperitoneal injection of streptozotocin (ACI) by high fat and sugar diet. Eighty models were randomly divided into diabetic model group, metformin hydrochloride 200 mg / kg group and lycopene , 20mg / kg), and another 16 rats of the same age were set as normal control group. The rats in each group were given gavage once daily for 4 weeks. After treatment, the fasting blood glucose level was measured by blood glucose meter, the body weight was measured and the kidney index was calculated. The urine output of 24h and the content of urinary protein (UPro) were measured, and the levels of blood urea nitrogen (BUN) ) And creatinine (SCr) were measured. The contents of total cholesterol (TC) and triglyceride (TG) in serum of rats in each group were measured. The levels of plasma C-reactive protein (CRP), tumor necrosis The levels of TNF-α, IL-1β, IL-6 and ICAM-1 were determined by enzyme-linked immunosorbent assay (ELISA) The expressions of AKT, bax and bcl-2 mRNA in the tissues were calculated and the ratio of bax / bcl-2 was calculated. The histopathological changes of renal tissues were observed by PAS staining. Results: Compared with diabetic model group, the body weight of rats in the treatment of lycopene 10 and 20 mg / kg was significantly increased, the index of kidney was significantly reduced, and the fasting blood glucose level of 20 mg / kg treatment group was significantly reduced. Lycopene 10 and 20 The content of BUN and SCr in serum of the rats in the treatment group were significantly decreased and UPro was significantly decreased, the levels of BUN and SCr in the serum were significantly decreased, while the content of TC and TG in the treated group were significantly decreased. The levels of CRP, The levels of bax mRNA and bcl-2 mRNA in kidney tissue of lycopene 10 and 20 mg / kg treatment groups were significantly decreased, while the levels of bax / The ratio of bcl-2 was significantly decreased. The AKT mRNA expression in 20 mg / kg treatment group was significantly increased. The glomerular and renal pathological changes in lycopene treatment group were significantly improved, especially in 20 mg / kg treatment group. CONCLUSION: Lycopene can reduce blood glucose, improve blood lipid, decrease the level of inflammatory mediators, decrease the intercellular adhesion molecule and improve the renal tissue pathology in a dose-dependent manner, suggesting that lycopene dose-dependently inhibits the inflammation of kidney in diabetic rats effect.
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