The purpose of this study was to determine the changes in the expression of sigma 1 receptors (σ1Rs) in the kidney of diabetic rats, which could indicate their possible role in the pathogenesis of diabetic nephropathy (DN). Sprague-Dawley rats were were given intraperitoneal injection of 55 mg/kg streptozotocin (STZ) in order to induce type I of diabetes (DM1). Control and diabetic rats were sacrificed 2 weeks or 2 months after DM1 induction. Expression of σ1Rs was determined in kidneys of the experimental rats, using immunohistochemistry.

The most prominent expression of σ1Rs was found in distal tubuli (DT). Results have shown significant increase in renal σ1Rs section percentage area of rats 2 months after DM1 induction, compared to both control group at the same age and diabetic group 2 weeks after induction (P < 0.01 both). Similarly, a number of immunoreactive DT increased in diabetic group 2 months after induction, compared to DM1 group 2 weeks after induction (P < 0.001). We also found a decrease of a number of immunoreactive DT 2 weeks post DM1 induction (P < 0.01). However, the same was found during maturation of the control rats (P < 0.001). In addition, a strong co-expression of σ1R and proinflammatory factor TGFβ was seen in vacuolated DT.

The results indicate to the potential role of σ1Rs in postnatal maturation of the rat kidneys and in distal tubular damage in the pathogenesis of the diabetic nephropathy. We conclude that σ1Rs could be potential target in treatment of the diabetic nephropathy.

本研究的目的是确定糖尿病大鼠肾脏中σ1受体（σ1Rs）表达的变化，这可能表明它们在糖尿病肾病（DN）发病机制中的可能作用。 Sprague-Dawley大鼠腹腔注射55 mg/kg链脲佐菌素(STZ)以诱导I型糖尿病(DM1)。 DM1 诱导后 2 周或 2 个月处死对照大鼠和糖尿病大鼠。使用免疫组织化学测定实验大鼠肾脏中 σ1Rs 的表达。

σ1Rs 最显着的表达出现在远端肾小管 (DT) 中。结果显示，DM1 诱导后 2 个月，与同龄对照组和诱导后 2 周糖尿病组相比，大鼠肾 σ1Rs 截面百分比面积显着增加（均 P < 0.01）。同样，与诱导后 2 周的 DM1 组相比，糖尿病组诱导后 2 个月的免疫反应性 DT 数量有所增加 (P < 0.001)。我们还发现 DM1 诱导后 2 周，免疫反应性 DT 数量减少（P < 0.01）。然而，在对照大鼠的成熟过程中也发现了同样的情况（P < 0.001）。此外，在空泡 DT 中观察到 σ1R 和促炎因子 TGFβ 的强烈共表达。

结果表明 σ1Rs 在大鼠肾脏出生后成熟和糖尿病肾病发病机制中远端肾小管损伤中的潜在作用。我们得出结论，σ1Rs 可能是治疗糖尿病肾病的潜在靶点。