Bei Weijian, Wang Yujiao, Chen Jianmei, Zhang Jingjing, Wang Lexun, Gu Zhanhui, Hu Yinming, Huang Yijian, Xu Wei, Lei Zili, Cai Jinyan, Guo Jiao
Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory against Metabolic Diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China.
Guangzhou University of Chinese Medicine, Guangzhou, China.
Evid Based Complement Alternat Med. 2019 Mar 3;2019:6378786. doi: 10.1155/2019/6378786. eCollection 2019.
To investigate the effect of FTZ on high-glucose-induced oxidative stress and underlying mechanisms.
We used a cell dysfunction and diabetes model that was induced in rats fed a high-fat high-sugar diet (HFHSD) for 6 weeks and injected once with 35 mg/kg streptozocin (STZ). Then, 3 and 6 g/kg of FTZ were administered by gavage for 8 weeks. In addition, an ex vivo model of oxidative stress was induced by stimulating INS-1 cells with 25 mmol/L glucose for 48 h.
The levels of fasting blood glucose (FBG) in diabetic model rats were obviously higher than those in the normal group; furthermore with reduced levels of cells, catalase (CAT), superoxide dismutase (SOD), and Bcl-2 increased lipid peroxide malondialdehyde (MDA) and caspase-3 in the pancreatic tissue of the diabetic model rats. Afterward, the cells were incubated with FTZ-containing serum and edaravone. The 25 mmol/L glucose-induced SOD reduction increased MDA and intracellular ROS. The protein expression level of Mn-SOD and CAT in the model group decreased significantly compared with that in the control group.
FTZ treatment significantly improved the alteration in the level of SOD, CAT, Bcl-2, caspase-3, and MDA coupled with cell dysfunction in diabetic rats. Oxidative stress in INS-1 cells was closely associated with a higher rate of apoptosis, increased production of ROS and MDA, enhanced Bax expression, and caspase-3, -9 activities and markedly decreased protein expression of Mn-SOD and CAT. FTZ-containing serum incubation notably reversed the high-glucose-evoked increase in cell apoptosis, production of ROS and MDA, and Bax protein levels. Furthermore, FTZ stimulation upregulated the expression levels of several genes, including Mn-SOD, CAT, and Bcl-2/Bcl-xl. In addition, FTZ decreased the intracellular activity of caspase-3, -9 in INS-1 cells. FTZ protected -cells from oxidative stress induced by high glucose in vivo and in vitro. The beneficial effect of FTZ was closely associated with a decrease in the activity of caspase-3, -9 and intracellular production of ROS, MDA, and Bax coupled with an increase in the expression of Mn-SOD, CAT, and Bcl-2/Bcl-xl.
探讨复方中药（FTZ）对高糖诱导的氧化应激的影响及其潜在机制。
我们采用一种细胞功能障碍和糖尿病模型，该模型通过给大鼠喂食高脂高糖饮食（HFHSD）6周并一次性注射35mg/kg链脲佐菌素（STZ）诱导而成。然后，通过灌胃给予3g/kg和6g/kg的FTZ，持续8周。此外，通过用25mmol/L葡萄糖刺激INS-1细胞48小时诱导体外氧化应激模型。
糖尿病模型大鼠的空腹血糖（FBG）水平明显高于正常组；此外，糖尿病模型大鼠胰腺组织中的细胞水平降低，过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和Bcl-2减少，脂质过氧化物丙二醛（MDA）和半胱天冬酶-3增加。随后，将细胞与含FTZ的血清和依达拉奉一起孵育。25mmol/L葡萄糖诱导的SOD降低增加了MDA和细胞内活性氧（ROS）。与对照组相比，模型组中Mn-SOD和CAT的蛋白表达水平显著降低。
FTZ治疗显著改善了糖尿病大鼠中SOD、CAT、Bcl-2、半胱天冬酶-3和MDA水平的改变以及细胞功能障碍。INS-1细胞中的氧化应激与较高的凋亡率、ROS和MDA的产生增加、Bax表达增强以及半胱天冬酶-3、-9活性显著相关，且Mn-SOD和CAT的蛋白表达明显降低。含FTZ血清孵育显著逆转了高糖引起的细胞凋亡增加、ROS和MDA产生以及Bax蛋白水平升高。此外，FTZ刺激上调了包括Mn-SOD、CAT和Bcl-2/Bcl-xl在内的几种基因的表达水平。此外，FTZ降低了INS-1细胞中半胱天冬酶-3、-9的细胞内活性。FTZ在体内和体外保护细胞免受高糖诱导的氧化应激。FTZ的有益作用与半胱天冬酶-3、-9活性降低以及细胞内ROS、MDA和Bax产生减少以及Mn-SOD、CAT和Bcl-2/Bcl-xl表达增加密切相关。
