| Chronic Kidney Disease(CKD) is a worldwide public health issue with increased morbidity as well as mortality. Nowadays, due to the complex mechanism of CKD, the clinical medicine treatment of CKD is not effective, and the financial burden of surgical therapy is too high, the economic and effective treatment method is not found. Traditional Chinese Medicine(TCM) has important significance for treatment of CKD, it can prolong the life of the remaining nephrons, improve the function of kidney and enhance the quality of life of patients from the early stage of active intervention. Shen-Kang injection(SK) is widely used as a clinical medicine of TCM. A large number of clinical trials had confirmed SK showed protective function in renal diseases, postponed the progression of CKD and protected of residual renal function. However, the mechanism of the renal protective function and the medicinal substances of SK are poorly understood, the clinical application is limited. Therefore, the purpose of the present study is to investigate the protective properties of SK as well as the detected effective substances of SK on CKD invivo and in vitro.Part 1:Aims To investigate the pharmacological effects of SK for CKD.Methods A rat model of CKD was created by 5/6 nephrectomy(5/6 Nx). The 36 male SD rats were randomly divided into six groups, sham group, model group, SK with three doses groups and positive group. SK or Enalapril was treated daily for one week after 5/6 Nx surgery, and blood was collected periodically from the orbit of SD rats. Animals were sacrificed at day 30 post surgery, blood and renal tissues were collected. The level of Blood urea nitrogen(BUN) and creatinine(SCr) were examined, and these kidney tissues were stained with hematoxylin and eosin to check the histopathology.Results After one week of treatment, SK significantly decreased the levels of SCr and BUN, and histological findings also showed noteworthy amelioration of the damaged renal tissue.Conclusions SK can alleviate the 5/6 Nx renal damage, it has a protective effect on CKD.Part 2:Aims To investigate the protective effects of SK or Rhein on CKD, the antioxidant and anti-inflammatory mechanism were determined.Methods ROS model was formed by hydrogen peroxide(H2O2) induced human renal proximal tubular(HK-2) cell, inflammation model was formed by Lipopolysaccharide(LPS) induced HK2 cell. Cell viability and apoptotic events were measured, and the levels of ROS and TAC or TNF-α, IL-6 and MCP-1 were detected, respectively. Meanwhile, the protein expression of mitogen-activated protein kinases(MAPKs) and uclear factor-κB(NF-κB) were determined by western blot, respectively.Results Treatment with SK or Rhein significantly recovered the decreased cell viability and the increased percentage of apoptotic cells, which was induced by H2O2 or LPS treatment. And the production of oxidative stress signaling molecules(ROS and TAC) and inflammatory signaling molecules(TNF-α, IL-6 and MCP-1) were reversed by SK and Rhein. Furthermore, the increased protein expression of phosphor-ERK, phosphor-JNK and phosphor-P38 MAPK and phosphor-IκBα were counter-regulated by SK and Rhein treatment.Conclusions SK and Rhein have a protective effect on CKD, and the MAPK and NF-κB signaling pathway may be involved in inhibiting oxidative stress damage and inflammation damage, respectively. |
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