Objective: To explore the effect and mechanism of bamboo leaf flavonoids on depression in type 2 diabetic rats. Methods: The streptozotocin (STZ) was used to induce the depression model of type 2 diabetic rats. Eight weeks old male Sprague-Dawley (SD) rats were randomly divided into 5 groups: the normal control group (n=8), the model group (n=9), the bamboo leaf flavonoid group (n=9), the solvent control group (n=9) and the bamboo leaf flavonoid normal control group (n=8). Rats of the bamboo leaf flavonoid group and the bamboo leaf flavonoid normal control group were treated with intragastric administration of bamboo leaf flavonoids (200 mg·kg(-1)·d(-1)) for 12 weeks. Tail suspension test (TST) and forced swimming test (FST) were used to measure the level of depression. Nissl staining was used to detect the survival amount of hippocampus neurons. The levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of receptor of advanced glycation endproducts (RAGE), phosphorylated signal protein P38 (p-P38), cleaved caspase-3 and the nuclear factor-κB (NF-κB) were detected by Western blotting. Results: Compared with the normal control group, the TST and FST immobility time of the model group rats increased [(206±13) s vs (101±9) s, (192±24) s vs (98±8) s, both P<0.01]. Furthermore, the injury of hippocampal neurons was more severe, and the boundary was unclear. The nissl bodies were scarce or disappeared, and nuclear pyknosis was observed. The levels of hippocampal CA3 IL-1β and IL-6 elevated [(31.78±4.12) pg/ml vs (9.26±3.52) pg/ml, (49.15±3.47) pg/ml vs (19.63±2.18) pg/ml, both P<0.01]. The Western blotting showed that the expressions of RAGE, p-P38, cleaved caspase-3 enhanced and NF-κB nuclear translocation increased (all P<0.05). After bamboo leaf flavonoids treatment (for 12 weeks), compared with the model group, the immobility time of TST and FST reduced in the bamboo leaf flavonoid group [(152±11) s vs (206±13) s, (110±19) s vs (192±24) s, P<0.01], and hippocampal neuronal injury alleviated. In addition, the concentrations of IL-1β and IL-6 decreased [(21.79±3.95) pg/ml vs (31.78±4.12) pg/ml, (34.68±4.28) pg/ml vs (49.15±3.47) pg/ml, both P<0.01] and the expressions of RAGE, p-P38, nuclear NF-κB, cleaved caspase-3 up-regulated in the bamboo leaf flavonoid group. Conclusion: Bamboo leaf flavonoids can effectively improve depression in diabetic rats through decreasing hippocampal neuronal injury and the release of inflammatory factors, and inhibiting RAGE/P38/NF-κB signaling pathway.
目的：研究竹叶黄酮对2型糖尿病大鼠抑郁的影响及机制。 方法：制备链脲佐菌素（STZ）诱导的2型糖尿病大鼠抑郁模型，雄性8周龄SD大鼠随机数字表法分为正常对照组（n=8）、模型组（n=9）、竹叶黄酮组（n=9）、溶剂对照组（n=9）、竹叶黄酮对照组（n=8）。竹叶黄酮组和竹叶黄酮对照组以竹叶黄酮（200 mg·kg(-1)·d(-1)）灌胃给药12周。悬尾试验（TST）和强迫游泳试验（FST）检测竹叶黄酮对2型糖尿病大鼠抑郁的影响，尼氏染色检测竹叶黄酮对2型糖尿病大鼠海马神经元损伤的影响，酶联免疫吸附法（ELISA）检测海马CA3区白细胞介素（IL）-1β、IL-6水平，Western印迹法检测海马CA3区晚期糖基化终末产物受体（RAGE）、磷酸化信号蛋白P38（p-P38）、活化型半胱氨酸天冬氨酸蛋白酶-3（caspase-3）的表达和核因子-κB（NF-κB）核转录水平。 结果：与正常对照组相比，模型组大鼠TST[（206±13）s比（101±9）s，P<0.01]和FST[（192±24）s比（98±8）s，P<0.01]不动时间均增加；海马神经元损伤较重，边界不清楚，尼氏小体稀少或消失，可见核固缩；海马CA3区IL-1β和IL-6水平均升高[（31.78±4.12）pg/ml比（9.26±3.52）pg/ml，（49.15±3.47）pg/ml比（19.63±2.18）pg/ml，均P<0.01]；RAGE、p-P38、活化型caspase-3和NF-κB表达水平升高（均P<0.05）。给予竹叶黄酮12周后，与模型组比较，竹叶黄酮组大鼠TST[（152±11）s比（206±13）s，P<0.01]和FST[（110±19）s比（192±24）s，P<0.01]的不动时间减少，海马神经元损伤减轻，海马CA3区IL-1β和IL-6炎性因子减少[（21.79±3.95）pg/ml比（31.78±4.12）pg/ml，（34.68±4.28）pg/ml比（49.15±3.47）pg/ml，均P<0.01）]，RAGE、p-P38、NF-κB和活化型caspase-3的表达水平降低。 结论：竹叶黄酮可改善2型糖尿病大鼠抑郁样行为，可能与减轻海马神经元损伤，减少炎性因子，抑制RAGE/P38/NF-κB信号通路有关。.
Keywords: Depression; Diabetes mellitus, type 2; Flavonoids; Hippocampus; Rats.