Zhang Yu-Fei, Meng Na-Na, Li Hou-Zhong, Wen Yi-Jie, Liu Jie-Ting, Zhang Chun-Lei, Yuan Xiao-Huan, Jin Xiu-Dong
Department of Physiology， School of Basic Medical Sciences， Heilongjiang University of Traditional Chinese Medicine， Harbin 150040， China.
Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy， Mudanjiang Medical University， Mudanjiang 157011， China.
Zhongguo Zhong Yao Za Zhi. 2018 Feb;43(3):596-602. doi: 10.19540/j.cnki.cjcmm.2018.0013.
To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS)， the male SD rats were intraperitoneally injected with streptozotocin(STZ， 60 mg·kg⁻¹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR)， the low-dose Nar group(Nar25)， the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25， Nar50， Nar100 groups were orally administered with Nar at the doses of 25.0， 50.0， 100.0 mg·kg⁻¹ per day， respectively， while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatment， fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78)， C/EBP homologous protein(CHOP)， cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the results， compared with control group， the myocardial structure was damaged， the content of MDA was increased， while the activities of SOD were decreased(<0.05) in T1DR group. GRP78， CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(<0.05， <0.01). Compared with T1DR group， myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreased， while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78， CHOP and caspase 12 were increased， especially in middle and high-dose groups(<0.05， <0.01). After treatment with Nar for 8 weeks， myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreased， while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78， CHOP and caspase 12 were increased， especially in middle and high-dose groups(<0.05， <0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.
为探讨柚皮苷（Nar）对链脲佐菌素（STZ）诱导的糖尿病大鼠心肌组织损伤的保护作用及其与氧化应激和内质网应激（ERS）的关系，将雄性SD大鼠腹腔注射链脲佐菌素（STZ，60 mg·kg⁻¹）建立糖尿病大鼠模型，然后随机分为1型糖尿病大鼠组（T1DR）、低剂量Nar组（Nar25）、中剂量Nar组（Nar50）和高剂量Nar组（Nar100）。将正常大鼠设为对照组（Con）。Nar25、Nar50、Nar100组分别按25.0、50.0、100.0 mg·kg⁻¹的剂量每日灌胃给予Nar，而正常组和T1DR组灌胃给予生理盐水。治疗8周后，测定空腹血糖和心脏质量指数。通过显微镜观察心肌组织的病理变化。测定心肌丙二醛（MDA）水平和超氧化物歧化酶（SOD）活性。采用qRT-PCR和Western blot检测葡萄糖调节蛋白78（GRP78）、C/EBP同源蛋白（CHOP）、半胱氨酸天冬氨酸特异性蛋白酶12（caspase 12）的基因和蛋白表达。结果显示，与对照组相比，T1DR组心肌结构受损，MDA含量增加，SOD活性降低（<0.05）。T1DR组GRP78、CHOP和caspase 12 mRNA及蛋白表达显著增加（<0.05，<0.01）。与T1DR组相比，Nar治疗组心肌结构损伤减轻。MDA含量降低，SOD活性显著增加。GRP78、CHOP和caspase 12的mRNA和蛋白表达增加，尤其是中、高剂量组（<0.05，<0.01）。Nar治疗8周后，Nar治疗组心肌结构损伤明显减轻。心肌组织中MDA含量降低，SOD活性显著增加。GRP78、CHOP和caspase 12的mRNA和蛋白表达增加，尤其是中、高剂量组（<0.05，<0.01）。研究结果表明，Nar可能通过减轻线粒体氧化应激损伤和抑制ERS介导的细胞凋亡途径来保护糖尿病大鼠的心肌。
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