丹栀降糖胶囊降低高脂饮食和链脲佐菌素所致糖尿病大鼠肾损伤,下调toll样受体4-核因子-κB通路及细胞凋亡。

Xie Jing, B I Zheng, Wang Sihai, Shen Guoming, Fang Zhaohui
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摘要

目的:探讨丹栀降糖胶囊(DJC)对链脲佐菌素(STZ)诱导的糖尿病大鼠肾损伤的影响及其机制。方法:采用高脂饲料喂养sd大鼠6周后注射链脲佐菌素(STZ, 35 mg/kg)。然后每天给予270、540和1080 mg/kg的姜黄酮治疗,连续8周。结果:高脂饮食加STZ可显著提高大鼠血糖、肌酐、尿素氮和尿白蛋白。同时观察高脂饮食大鼠注射STZ后肾小球和肾小管病变情况。这些生化和病理变化在ddc处理下呈剂量依赖性明显减弱。在机制上,DJC处理显著降低了高脂饲料喂养和STZ注射大鼠肾脏中toll样受体4 (TLR4)、丝裂原活化蛋白激酶(MAPK)和核因子-κB (NF-κB)信号。末端脱氧核苷酸转移酶dUTP缺口末端标记染色和caspase-8水平显示,高脂饮食和STZ注射大鼠肾细胞凋亡增加,而ddc治疗可减轻这种情况。结论:DJC治疗对糖尿病肾病具有保护作用,其机制可能与下调TLR4/MAPK/NF-κB通路及细胞凋亡密切相关。本研究提供了进一步的证据,证明使用ddc作为糖尿病肾病的潜在治疗选择。
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Danzhi Jiangtang capsule reduces renal injury in rats with diabetes induced by high fat diet and streptozotocin downregulating toll-like receptor 4-nuclear factor-κB pathway and apoptosis.

Objective: To investigate the effect and mechanisms of Danzhi Jiangtang capsule (, DJC) on renal injury in streptozotocin (STZ)-induced diabetes of rats.

Methods: Sprague-Dawley rats were fed with high fat diet for 6 weeks followed by streptozotocin (STZ, 35 mg/kg) injection. These rats were then treated with DJC (270, 540 and 1080 mg/kg) daily for 8 weeks.

Results: A combination of high fat diet and STZ significantly increased blood glucose creatinine, urea nitrogen, and urine albumin in rats. Meanwhile, the glomerular and tubular lesions were observed in rats fed with high fat diet and injected with STZ. These biochemical and pathological changes were significantly attenuated by DJC treatments in a dose-dependent manner. Mechanistically, DJC treatments significantly decreased toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signals in the kidney of rats fed with high fat diet and injected with STZ. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining and caspase-8 levels showed that renal apoptosis was increased in rats fed with high fat diet and injected with STZ, and this was attenuated by DJC treatments.

Conclusions: DJC treatments protect against diabetic kidney disease, and the mechanism may be closely related to downregulation of TLR4/MAPK/NF-κB pathways and apoptosis. This study provides further evidence of using DJC as a potential therapeutic option for diabetic kidney disease.

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