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(n=10)

DN model(n=12)

EA(n=11)

EA+inhibitor(AS1842856 targeting FoxO1

n=11) and inhibitor(n=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. Results Compared with the normal control group

the levels of body mass

SOD activity

and FoxO1 and PGC-1α protein expression were significantly reduced(P<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(P<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(P<0.01

P<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(P<0.01

P<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(P<0.05

P<0.01)

and in down-regulating blood glucose

BUN

ALB and ROS levels(P<0.05

P<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. 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.