富含生育三烯酚的馏分 (TRF) 可防止链脲佐菌素诱导的糖尿病视网膜病变大鼠的视网膜细胞凋亡，并维持其视觉行为。
Tocotrienol-rich fraction (TRF) protects against retinal cell apoptosis and preserves visual behavior in rats with streptozotocin-induced diabetic retinopathy.
机构信息
School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia.
Department of Pharmacology, Faculty of Medicine, Manipal University College Malaysia, Bukit Baru, Melaka, 75150, Malaysia.
出版信息
BMC Complement Med Ther. 2024 Aug 30;24(1):322. doi: 10.1186/s12906-024-04614-y.
BACKGROUND
Tocotrienol is a vitamin E analogue that is known to exert anti-inflammatory and antioxidant effects. Hence, in the current study, the effects of TRF on the expression of pro- and anti-apoptotic proteins in the streptozotocin-induced diabetic rat retinas were investigated. The effect of TRF on the visual behaviour of rats was also studied.
METHODS
Diabetes was induced in rats by intraperitoneal injection of streptozotocin and was confirmed by a blood sugar level of at least 20 mmol/L, 48 h, post-injection. Diabetic rats were divided into a group treated with vehicle (DV) and the other treated with TRF (100 mg/kg; DT). A group of non-diabetic rats treated with vehicle (N) served as the control group. All treatments were administered orally for 12 weeks. Rats were then subjected to an assessment of general behaviour in an open field arena and a two-chamber mirror test to assess their visual behaviour. At the end of the experimental period, rats were sacrificed, and their retinas were isolated to measure the expression of pro- (Casp3, Bax) and anti-apoptotic (Bcl2) markers using RT-qPCR and ELISA. TUNEL staining was used to detect the apoptotic retinal cells.
RESULTS
Treatment with TRF lowered the retinal expression of Casp3 protein by 2.26-folds (p < 0.001) and Bax protein by 2.18-fold (p < 0.001) compared to vehicle-treated rats. The retinal anti-apoptotic protein Bcl2 expression was 1.87-fold higher in DT compared to DV rats (p < 0.001). Accordingly, the Bax/Bcl2 ratio in the TRF-treated group was significantly greater in DT compared to DV rats. Retinal Casp3, Bax, and Bcl2 gene expression, as determined by RT-qPCR, also showed changes corresponding to protein expression. In the open field test, DV rats showed greater anxiety-related behaviour than group N, while the behaviour of DT rats was similar to the N group of rats. DT rats and group N rats preferred the inverse mirror chamber over the mirror-containing chamber in the two-mirror chamber test (p < 0.01).
CONCLUSION
Oral TRF therapy for 12 weeks lowers retinal cell apoptosis by decreasing pro- and increasing anti-apoptotic markers. The preservation of visual behaviour in a two-chamber mirror test supported these retinal molecular alterations in diabetic rats.
背景
生育三烯酚是一种维生素 E 类似物，已知具有抗炎和抗氧化作用。因此，在本研究中，研究了 TRF 对链脲佐菌素诱导的糖尿病大鼠视网膜中促凋亡和抗凋亡蛋白表达的影响。还研究了 TRF 对大鼠视觉行为的影响。
方法
通过腹腔注射链脲佐菌素诱导大鼠糖尿病，注射后 48 小时血糖水平至少 20 mmol/L 即可确认。将糖尿病大鼠分为用载体（DV）治疗的一组和用 TRF（100mg/kg；DT）治疗的另一组。一组用载体（N）治疗的非糖尿病大鼠作为对照组。所有治疗均通过口服给药 12 周。然后，将大鼠置于开放场竞技场中进行一般行为评估，并进行双室镜测试以评估其视觉行为。在实验期末，处死大鼠，分离其视网膜，使用 RT-qPCR 和 ELISA 测量促凋亡（Casp3、Bax）和抗凋亡（Bcl2）标志物的表达。使用 TUNEL 染色检测凋亡的视网膜细胞。
结果
与载体处理的大鼠相比，TRF 处理降低了 Casp3 蛋白的视网膜表达 2.26 倍（p<0.001）和 Bax 蛋白的视网膜表达 2.18 倍（p<0.001）。与 DV 大鼠相比，DT 大鼠的视网膜抗凋亡蛋白 Bcl2 表达高 1.87 倍（p<0.001）。因此，与 DV 大鼠相比，TRF 处理组的 Bax/Bcl2 比值显著更高。通过 RT-qPCR 确定的视网膜 Casp3、Bax 和 Bcl2 基因表达也显示出与蛋白表达相对应的变化。在开放场测试中，与 N 组相比，DV 大鼠表现出更大的焦虑相关行为，而 DT 大鼠的行为与 N 组大鼠相似。在双室镜测试中，DT 大鼠和 N 组大鼠更喜欢倒置镜室而不是带镜的镜室（p<0.01）。
结论
口服 TRF 治疗 12 周可通过降低促凋亡标志物和增加抗凋亡标志物来降低视网膜细胞凋亡。在双室镜测试中保留视觉行为支持了糖尿病大鼠视网膜分子变化。
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