Department of Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, People's Republic of China.
Precision Medicine Centre, Yijishan Hospital of Wannan Medical College, Wuhu, People's Republic of China.
Drug Des Devel Ther. 2020 Dec 31;14:5773-5782. doi: 10.2147/DDDT.S257734. eCollection 2020.
Tanshinone IIA (Tan IIA), a compound extracted from , can improve type II diabetes, while the molecular mechanisms underlying Tan IIA-mediated protective effects in diabetic nephropathy are unclear. This study explored the protective actions of Tan IIA on renal tissues in streptozotocin (STZ)-induced diabetic nephropathy.
Tan IIA (2, 4, 8 mg/kg/day) was daily administered to STZ-treated rats by intraperitoneal injection for 42 days. The morphologic pathology was evaluated by hematoxylin-eosin and Masson's trichrome staining, and transmission electron microscopy. The protein expression levels in renal tissues were evaluated by Western blotting and immunohistochemistry; the mRNA expression level was determined by quantitative real-time PCR.
Tan IIA at 2 and 4 mg/kg attenuated the increase in the levels of uric acid and blood urea nitrogen and restored the reduction in the superoxide dismutase activity in the serum of the diabetic rats. Tan IIA at 2 and 4 mg/kg, but not 8 mg/kg, ameliorated the thickening of renal tubule in the diabetic rats; Tan IIA at 2 and 4 and 8 mg/kg attenuated the thickening of glomerular basement membrane and the collagen deposition in the renal tissues of the diabetic rats. Tan IIA treatment at 2, 4, 8 mg/kg decreased the expression levels of transforming growth factor-beta1, TSP-1, Grp78 and CHOP in the diabetic rats. Tan IIA at 2 and 4 and 8 mg/kg attenuated the increase in the protein levels of p-PERK, p-elf2α and ATF-4 from the renal tissues of diabetic rats, while the protein level of AFT-6 and the mRNA expression levels of XBP-1t, XBP-1s and p58IPK in the renal tissues were not affected by STZ or Tan IIA treatment.
Tan IIA-mediated protective effects on the STZ-induced diabetic nephropathy may be associated with the reduced endoplasmic reticulum stress via attenuating PERK signaling activities.
丹参酮 IIA（Tan IIA）是从丹参中提取的一种化合物，可改善 2 型糖尿病，但其介导的糖尿病肾病保护作用的分子机制尚不清楚。本研究探讨了 Tan IIA 对链脲佐菌素（STZ）诱导的糖尿病肾病肾组织的保护作用。
Tan IIA（2、4、8mg/kg/天）通过腹腔注射每天给予 STZ 处理的大鼠，共 42 天。苏木精-伊红和 Masson 三色染色以及透射电子显微镜评估形态病理学。通过 Western blot 和免疫组织化学评估肾组织中的蛋白表达水平；通过定量实时 PCR 确定 mRNA 表达水平。
Tan IIA（2 和 4mg/kg）可降低糖尿病大鼠血清尿酸和血尿素氮水平的升高，并恢复超氧化物歧化酶活性的降低。Tan IIA（2 和 4mg/kg），但不是 8mg/kg，可改善糖尿病大鼠肾小管增厚；Tan IIA（2、4 和 8mg/kg）可减轻肾小球基底膜增厚和肾组织胶原沉积。Tan IIA 治疗（2、4、8mg/kg）可降低糖尿病大鼠转化生长因子-β1、TSP-1、Grp78 和 CHOP 的表达水平。Tan IIA（2、4 和 8mg/kg）可减轻糖尿病大鼠肾组织中 p-PERK、p-elf2α 和 ATF-4 蛋白水平的升高，而肾组织中 AFT-6 蛋白水平和 XBP-1t、XBP-1s 和 p58IPK 的 mRNA 表达水平不受 STZ 或 Tan IIA 治疗的影响。
Tan IIA 对 STZ 诱导的糖尿病肾病的保护作用可能与通过减轻 PERK 信号活性来减少内质网应激有关。
