OBJECTIVE: To observe the effect of electroacupuncture (EA) of combined "Biao"- and "Ben"-acupoint (for treating symptoms and root causes of the disease, respectively) on the expression of kidney forkhead box O1 (FoxO1) and peroxi-some proliferator-activated receptor-γ coactivator-1α (PGC-1α) in diabetic nephropathy (DN) rats, so as to explore its potential mechanisms underlying improvement of DN.
METHODS: Wistar rats were randomly divided into normal control (=10), DN model (=12), EA (=11), EA+inhibitor (AS1842856 targeting FoxO1,=11) and inhibitor (=11) groups. The DN model was established by high fat and high glucose diet for 6 weeks and intraperitoneal injection of streptozotocin (55 mg/kg). EA (2 Hz, 1 mA) was applied to bilateral "Zusanli"(ST36), "Guanyuan"(CV4), "Fenglong" (ST40) and "Zhongwan"(CV12) for 15 min, once every other day for 8 weeks. The body mass was recorded, and blood glucose detected. The serum was sampled for detecting creatinine (Scr) content with Jaffe's assay, urea nitrogen (BUN) content with urease method. Urine albumin (ALB) and renal reactive oxygen species (ROS) contents were detected with ELISA, renal superoxide dismutase (SOD) activity with xanthine oxidase method, and renal malondialdehyde (MDA) content with thiobarbituric acid method. The renal subcellular structure was observed under transmission electron microscopy, and the expression levels of PGC-1α and FoxO1 proteins in the kidney tissue were detected using Western blot. n n n n n
RESULTS: Compared with the normal control group, the levels of body mass, SOD activity, and FoxO1 and PGC-1α protein expression were significantly reduced (<0.01), while the contents of blood glucose, and serum Scr and BUN, urine ALB, renal MDA and ROS levels significantly increased in the model group (<0.01). In comparison with the model group, the levels of body mass, SOD activity, and FoxO1 and PGC-1α expression were significantly increased in the three treatment groups except SOD, expression of FoxO1 and PGC-1α in the inhibitor group (<0.01,<0.05), and the contents of blood glucose, Scr, BUN, ALB, MDA and ROS were obviously decreased in the three treatment groups except ALB and ROS in the inhibitor group (<0.01,<0.05). The therapeutic effect of EA was notably superior to that of EA+inhibitor and inhibitor in increasing body mass, SOD activity, and FoxO1 and PGC-1α expression levels (<0.05,<0.01), and in down-regulating blood glucose, BUN, ALB and ROS levels (<0.05,<0.01), suggesting a reduction of the therapeutic effect of EA after administration of the inhibitor AS1842856 of FoxO1. Results of electron microscopy showed diffusely thickened and vague basement membrane, increased mesangial matrix, fused foot process, and reduced volume of endothelial cells with pykno-tic nucleus of the kidney tissue in the model group, which was obviously milder in both EA and EA+inhibitor groups particularly in the EA group. P P P P P P P P P P
CONCLUSION: EA increases the expression of FoxO1 and PGC-1α in the kidneys of DN rats, thereby reducing the oxidative stress response and protecting the kidneys.
