| Nephrotoxicity induced by cisplatin was established in rats, observing the protective effects of Ligustrazine and investigate its action mechanism from the aspects of anti-oxidation damage and cell apoptosis. Nephrotoxicity in rats was induced to be impaired with single (ip) cisplatin dose of 8mgkg-1 body weight. Ligustrazine (50 mg·kg-1d-1\, 100 mg·kg-1d-1 body weight) was given two days before the cisplatin injection for five days. Then the rats were sacrificed four hours after the last injection. After the kidneys were removed to calculate the renal index, Blood urea nitrogen(BUN) and serum creatinine (Scr) was tested , urine samples obtained to find the content of 24 hours urinary protein and the activity of N-acetyl-|3-D-glucosaminidase(NAG), γ-Glutamyl-transpeptidase(GGT) and alkaline phosphatase(ALP). The content of malondial dehyde (MDA) and glutathione (GSH) content, anti-oxidase activities of superoxide dismutase (SOD) and glutathione-S-transferase (GST) in renal were detected. The content of nitric oxide (NO) and the activity of nitric oxide synthase(NOS) in renal cortex were measured . Rat kidneys were soaked in 10% formaldehyde solution and then embedded in paraffin. The tissue sections were stained with hematoxylin and eosin and lesions of glomerulus and tubules were observed under Optical microscope. Apoptosis was evaluated by terminal dexoynucleotidl transferase mediated d-UTP nick and labeling(TUNEL). Immunohis-tochemistry was used to detect the protein expression level of Bax and Bcl-2.The ligustrazine (50 mg·kg-1d-1, 100 mg·kg-1d-1 body weight) administration dose-dependently reduced content of 24h urinary protein, the content of BUN, Scr which been raised by cisplatin, the content of 24h urinary protein, the content of BUN, Scr was significantly decreased by 41%, 65%, 18% , 58%, 14%, 49% (P<0.05, p<0.01) respectively;compared with the DDP group, the ligustrazine 100 mg·kg-1d-1 body weight administration significantly decreased the activity of urinary NAG, GGT, ALP by 17 %,29%, 46%. 48%, 18%, 25% (P<0.05. p<0.01) respectively. The ligustrazine dose of 100 mg-kg'^d^body weight can significant reduced the content of MDA . NO and activity of NOS in kidney which can increased by cisplatin.The content of MDA > NO and activity of NOS in kidney was significantly decreased by 37%, 45%, 23%( P < 0.05)respectively; the content of GSH and the activities of SOD. GST in TMP 100 mgkg'd"1 group were significantly increased by 1.33-fold, 1.66-fold , 1.57-fold (P <0.05) respectively compared with DDP group.The histopathological changes of kidney suggest that the serious congestion ofglomeruli > swelling of kidney tubules and the casts including protein casts and erythrocyte casts in DDP groups and ligustrazine can notably improve it. The results of TUNEL found more apoptotic cell in DDP group and the cells were focus on kidey tubules. Rats in DDP group show a much strong staining for Bax protein and a weaker staining of Bcl-2 than control group by means of .immunohistoc- hemistry .Ligstrazine can significant decling the number of apoptotic cells , increased the expression of Bcl-2 and decling the exprssion of Bax .And the Bax / Bcl-2 ratio was declined significantly by ligusrazine(p < 0.01).The results suggested that the Ligstrazine can protect the nephrotoxisity induced by cisplatin in rats and the mechanism of the protective effect may have some relationship with increasing the anti-oxidation ability of body -. reducing the lipid peroxidation level and refraining cell apoptosis.
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