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目的探讨4-苯基乙酸(4-PBA)对链脲佐菌素(STZ)诱导的1型糖尿病(T1DM)大鼠胰岛β细胞凋亡的保护作用。方法STZ(60 mg/kg)一次性腹腔注射建立T1DM大鼠模型(n=22),并将成功制备的14只T1DM大鼠(血糖持续1周≥16.7 mmol/L)随机分为2组:T1DM组和4-PBA治疗组各7只。另外取对照组10只,腹腔注射等量柠檬酸-柠檬酸钠缓冲液。4-PBA治疗组大鼠自造模成功第10天开始以40 g/L4-PBA[500 mg/(kg.d)]灌胃20 d,对照组和T1DM组大鼠予等量9 g/L盐水灌胃。观察各组大鼠体质量、血糖变化,处死后留取其血清和胰腺组织标本,测定血清胰岛素;光镜和脱氧核糖核苷酸末端转移酶介导的原位末端标记(TUNEL)法观察胰岛β细胞的形态学改变;反转录聚合酶链反应检测胰腺细胞基因Bax和Bcl-2 mRNA表达。结果T1DM大鼠血糖在4-PBA治疗后渐下降,但仍未降到正常水平。T1DM大鼠血清胰岛素水平降低,4-PBA治疗后血清胰岛素水平有所增加。光镜和TUNEL显示T1DM大鼠4-PBA治疗后减少了由STZ引起的胰岛β细胞的凋亡(P<0.05)。与对照组比较,T1DM组大鼠凋亡蛋白Bax mRNA显著上调(P<0.01),抗凋亡蛋白Bcl-2 mRNA显著下调(P<0.01)。结论4-PBA可减轻胰岛β细胞损害,使其不发生过度凋亡,从而降低血糖。
Objective To investigate the protective effect of 4-phenylacetate (4-PBA) on pancreatic β-cell apoptosis in streptozotocin (STZ) -induced type 1 diabetes mellitus (T1DM) rats. Methods T1DM rat model was established by intraperitoneal injection of STZ (60 mg / kg) (n = 22). Totally 14 T1DM rats (≥1.67 mmol / L) were randomly divided into two groups: There were 7 rats in T1DM group and 4-PBA treatment group. In addition, 10 rats in the control group were injected intraperitoneally with the same amount of citric acid-sodium citrate buffer solution. The rats in 4-PBA treatment group were given gavage for 40 days at the dose of 40 g / L 4-PBA [500 mg / (kg · d) L saline irrigation stomach. The changes of body weight and blood glucose of the rats in each group were observed, and the serum and pancreatic tissue specimens were collected after sacrifice, and the levels of serum insulin were measured. The islets were observed by light microscopy and deoxyribonucleotidyl transferase-mediated end-labeling (TUNEL) β cell morphology; reverse transcription polymerase chain reaction detection of pancreatic cell gene Bax and Bcl-2 mRNA expression. Results The blood glucose of T1DM rats gradually decreased after 4-PBA treatment, but still not dropped to the normal level. Serum insulin levels decreased in T1DM rats and serum insulin levels increased after 4-PBA treatment. Light microscopy and TUNEL showed that 4-PBA treatment of T1DM rats reduced pancreatic β-cell apoptosis induced by STZ (P <0.05). Compared with the control group, the apoptosis protein Bax mRNA of T1DM group was significantly increased (P <0.01) and the anti-apoptotic protein Bcl-2 mRNA was significantly decreased (P <0.01). Conclusion 4-PBA can reduce pancreatic β-cell damage, so that it does not occur excessive apoptosis, thereby reducing blood sugar.