Effects Of Nrf2 Signaling Pathway In Protection Of Grape Seed Procyanidins Extract On Oxidative Stress Of Kidney Induced By Lead In Rats

Lead(Pb) is a known heavy metal toxic substances, widely exists in the environment. There was study find that chronic Pb poisoning can make the levels of fre e radicals elevate in kidney, cause renal oxidative stress. Grape seed proanthocyanidin extract(GSPE) is nature polyphenol compounds that have many functions such as scavenging free radical, anti-oxidation, and anti-inflammation. The main purpose of this study was to clarify the protective effect of GSPE and the mechanism of Nrf2 signaling pathway in GSPE protecting the renal oxidative damage induced by Pb. This research will lay a basis on the effect of GSPE on the prevention and treatment of Pb exposure.Fouty healthy male wistar rats were randomly divided into 4 groups: control group, Pb group, Pb+GSPE group, and GSPE group, 10 rats per group. The study lasted 30 days, the control group drank water freely and gavage saline(1 m L/kg·day); Pb group drank 0.25% lead acetate(Pb Ac) solution freely and gavage saline(1 mL/kg·day); Pb+GSPE group 0.25% Pb Ac solution freely and gavage GSPE solution(200 mg/kg·day); GSPE group drank water freely and gavage GSPE solution(200 mg/kg·day). Then detection the index as follows:(1) Rats body and both of the kidney were weighed respectively, then calculated the kidney viscera index.(2) Rats blood were collected via abdominal aorta, centrifugalization, and the serum were used to detect the levels of serum creatinine(SCr) and blood urea nitrogen(BUN) by automatic biochemical analyzer.(3) Determination of Pb content in the kidney by Flame atomic absorption spectrometry.(4) Renal paraffin section,HE staining,histopathology of kidney were detected by microscope.(5) The level of superoxide dismutase(SOD), methane dicarboxylic aldehyde(MDA), glutathione(GSH), and glutathione s-transferase(GSH) in kidney tissue homogenate were tested.(6) Determinating the apoptotic in kidney by Terminal Deoxynucleoitidyl Transferase Mediated Nick-End Labeling(TUNEL).(7) The level of Nrf2 in kidney were detected by Immunohistochemistry.(8) Determinating the content of Nrf2, Keap1, HO-1, NQO1, Bax, Bcl-2, and Bcl-xl in the total protein extracted from kidney.The results show that:(1) GSPE can decrease the levels of SCr and BUN, effect to 10% and 31%, also reduce the elevated of viscera index induce by Pb, effect to 21%, and repair the tissue injury of renal.(2) GSPE can reduce the accumulation of Pb in renal, the effect can be 33%(3) GSPE has the ability of removal of oxygen free radicals, which increase content of SOD, GSH, and GST in renal, and decrease MDA level in renal.(4) GSPE can activate Nrf2 signaling pathway, increase the the expression of Nrf2 and phaseⅡdetoxification enzymes, then decrease apoptosis.These results suggest that GSPE can protect the nephrotoxicity and oxidative injury of rats induced by Pb, the main mechanism is that GSPE could activate Nrf2 signaling pathway, improve the level of antioxidant enzyme, and reduce cell apoptosis.