Abstract:

Objective To investigate the improvement effect of tetramethylpyrazine（TMP） on oxidative damage of kidney tissue in the nephrolithiasis model rats， and to clarify its possible mechanism. Methods A total of 40 healthy male SD rats were randomly divided into control group， model group， TMP group and positive control group. After pre-experiment，except control groups，the rats in other groups were intraperitoneally injected with 80 mg·kg^－1 glyoxylate stock solution to establish the rat models of kidney stones； the rats in TMP group were intraperitoneally injected with TMP hydrochloride injection 100 mg·kg^－1，the rats in positive control group were intragastrically perfused with 3.12 g·kg^－1 of Shenshitong granules， and the rats in control group were intraperitoneally injected with 2.5 mL·kg^－1 of 0.9% sodium chloride injection，lasted for 10 d.The rat kidney tissue sections were taken， Von Kossa staining and HE staining were performed to observe the calcium deposition and the pathomorphology of kidney tissue， and the levels of malondialdehyde（MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in kidney tissue of the rats in various groups were detected. Western blotting method was used to detect the expression levels of nuclear protein nuclear factor E2-related factor 2 （Nrf2）， holoprotein heme oxygenase-1 （HO-1） and NAD（P）H quinone oxidoreductase 1 （NQO1） proteins in kidney tissue of the rats in various groups. Results Compared with control group，obvious calcium deposition was seen in the Von Kossa staining of kidney tissue of the rats in model group，and the quantitative grading score of crystal was significantly increased （P<0.01）；the HE staining results showed obvious pathological damage in kidney tissue cells，the level of MDA in kidney tissue was significantly increased （P<0.01）， the activities of SOD and GSH-Px were significantly decreased （P<0.01），and the expression levels of Nrf2， HO-1 and NQO1 proteins in kidney tissue were significantly decreased （P<0.01）. Compared with model group， calcium deposition was seen in the Von Kossa staining of kidney tissue of the rats in TMP group and positive control group， and the quantitative grading scores of crystal were decreased （P<0.05）；the HE staining results showed that the pathological damage of kidney tissue cells was alleviated， the levels of MDA were significantly decreased （P<0.05），the activities of SOD and GSH-Px were significantly increased （P<0.05）， and the expression levels of Nrf2， HO-1 and NQO1 proteins in kidney tissue were significantly increased （P<0.05）. Conclusion Kidney stones can cause oxidative stress injury in the rat kidney tissue， resulting in the changes in oxidative stress indicators and Nrf2/antioxidant response element（ARE） signaling pathway protein expression levels in kidney tissue. TMP can activate this signaling pathway after intervention， so as to improve the oxidative stress injury of kidney tissue.

Key words: Tetramethylpyrazine, Kidney stones, Oxidative stress response, Nuclear factor E2-related factor 2, Antioxidant response element, Antioxidase