| Objective: To observe the effects of ginkgo biloba extract (GBE) on morphology and function of kidney of diabetic rats and further investigate the mechanism of GBE's protective effects on diabetic kidney.Methods: Thirty male Sprague-Dauley rats were randomly devided into three groups: 10 rats were taken as normal control, 10 as diabetic and 10 as GBE treated. The diabetic and GBE treated groups were injected intraperitoneally with strepozotocin at a dosage of 50mg/kg to induce diabetes mellitus. GBE was injected at a dosage of 8mg kg~-1d~-1 intraperitoneally in the GBE treated group for five weeks.The control and diabetic group were injected intraperitoneally with normal saline of equal volume for five weeks. Before the rats were sacrificed, the body weight, total urine volume and total urine protein of 24 hours were recorded. Blood glucose concentration,kidney weight and creatinine clearance rate were detected. The ultrastructural changes of the kidney tissue was studied by transmission electron microscopy. The activity of superoxide dismutase(SOD), nitric oxide synthase(NOS) and content of malondialdehyde(MDA), NO in the kidney homogenate were assayed by spectophotometer respectively. The mRNA expression of iNOS, nNOS, eNOS in kidney tissue was detected by RT-PCR.Results:1. Compared with the normal control group, diabetic group showed significantly higher blood glucose level, creatinine clearance rate (Ccr) and kidney hypertrophy index (expressed as kidney weight/body weight) (P<0.01). The 24 hour urinary protein excretion increased in diabetic group but showed no significant difference compared with that in normal control group (P>0.05). In GBE treated group, the blood glucose level and kidney hypertrophy index were significantly decreased (P<0.05) compared with those in diabetic group, but still higher than those in control group(P <0.05).2. Compared with the normal control group, the activitiy of SOD significantly decreased(P<0.05) while the content of NO, MDA and the activity of NOS significantly increased in diabetic group(P<0.05). In GBE treated group,the activity of SOD was significantly increased,the content of NO,MDA and the activity of NOS significantly decreased compared with those in diabetic one(P<0.05), but no significant difference was showed compared with those in control group (P>0.05).3. Compared with the normal control group, the mRNA expression of iNOS, eNOS significantly increased (P<0.01), but the expression of nNOS significantly decreased(P<0.01) in diabetic group. In GBE treated group, the mRNA expression of iNOS, eNOS were significantly decreased(P<0.01) while the expression of nNOS significantly increased(P<0.01) compared with those diabetic one(P<0.01). The mRNA expression of nNOS, eNOS showed no significant difference compared with those in normal control group (P>0.05), but the mRNA expression of iNOS was still showed higher than that in normal control one(P <0.05).4. The ultrastructural changes in kidney: It was manifested as thicken of glomerular basal membrane,swelling, shorten and confluence of foot process of podocyte, expansion of mitochondriae of parietal epithelium and increase of collagen of glomerulus in diabetic rats. In addition, it was showed swelling of microvilli and expansion of mitochondriae in the epithelium of glomerular tubule. But it was relieved in GBE treated group.Conclusion:1. GBE could increase the activity of SOD and decrease the content of MDA from kidney of diabetic rats, which may protect kidney from the damage caused by lipid peroxidation.2. GBE could inhibit mRNA expression of iNOS, eNOS,decrease the activity of NOS and production of NO, which may be related to improvement of glomerular high perfusion in the kidney of diabetic rats.3. GBE could ameliorative the hypertrophy of kidney,improve pathological change of kidney and retard the progress of diabetic nephropathy, the mechanism of protective effects of GBE on the kidney of diabetic rats may be related to its anti-lipid peroxidation and inhibiting the production of NO. |
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