| Objective:To study the effect and mechanism of Dilongjiangya capsule on early renal damage in Spontaneously Hypertensive Rats based on AngII-TLR4/NF-?B pathway.Methods:Forty male SHRs without specific pathogens?SPF?were used.According to the systolic blood pressure value,they were randomly divided into model group?equal volume distilled water gavage?and Dilongjiangya capsule low-dose,middle-dose and high-dose groups?Dilongjiangya capsule 126mg/kg,252mg/kg,504mg/kg,respectively gavage?,benazepril group?benazepril hydrochloride 0.9mg/kg gavage?,8 rats in each group;Eight SPF-grade co-weekly male homogenous normotensive rats were used as normal control group and were given distilled water with equal volume.Rats in each group were given intragastric administration once daily for 60 days.Systolic blood pressure and diastolic blood pressure were measured before and at 12,24,36,48,and 60 days after administration.At the end of the experiment,24 hours urine was collected from the rats,blood serum was collected,and kidneys were taken.The levels of mAlb and NAG in rat urine were measured by ELISA.The levels of serum?2-MG,CysC,and AngII were determined by ELISA.The levels of BUN in serum were determined by urease method,and the CRE content in serum was measured by sarcosine oxidation.Colorimetry was used to measure the serum UA level.Microscopy was used to observe the histological changes of rat kidneys with HE staining.The ultrastructure of rat kidneys was observed by transmission electron microscope.The expression of TLR4,NF-?B-p65,TNF-?and IL-10 proteins in rat kidneys was detected by immunohistochemistry.The expression of TLR4,NF-?B-p65,TNF-?and IL-10 protein in rat renal tissue was detected by Western blotting.Rseults:?1?Blood pressure and early renal impairment index:Compared with the normal control group,the systolic blood pressure and diastolic blood pressure of the model group rats increased significantly?P<0.05?before and at 12,24,36,48,and 60 days after administration.At 60 days,the levels of urine mAlb and NAG increased?P<0.05?,and the levels of serum?2-MG and Cys C increased in the model group?P<0.05?.Compared with the model group,the systolic blood pressure decreased significantly at the 36th,24th,12th,and 12th days after administration of low-dose group,middle-dose group,high-dose group,and benazepril group?P<0.05?.Diastolic blood pressure was significantly decreased on the 60th,36th,24th,and12th days after administration?P<0.05?.At 60 days,the levels of urine mAlb and NAG were decreased in each dose group of Dilongjiangya capsule and benazepril group?P<0.05?.The serum of rats in Dilongjiangya capsules,high-dose group and benazepril group were decreased.The levels of?2-MG and CysC were decreased?P<0.05?,suggesting that Dilongjiangya Capsule can reduce blood pressure and improve early kidney damage in Spontaneously Hypertensive Rats with dose-dependent manner.?2?Kidney tissue HE staining:normal control group rats glomerular,tubular structure is normal;model group of parts of the rat kidney glomerular cavity with mild stenosis with irregular,mild glomerular mesangial cells Hyperplasia and mesangial matrix increased,and renal tubular epithelial cells were slightly edematous.After administration of Dilongjiangya capsule and benazepril,renal histopathological changes were also observed,but the extent of lesions was alleviated.Transmission electron microscopy of renal tissue:There was no abnormality in the ultrastructure of the kidney in the normal group;in the model group,the podocyte foot processes of the glomerular segments of the glomerular were significantly fused,the endothelial cells were swollen,and the electron density of the capillary lumen was decreased.Mesangial cells increased significantly,mesangial area widened,and mesangial matrix severely proliferated;the above-mentioned performance was improved to varying degrees after giving Dilongjiangya capsule and benazepril.?3?Pathway indicators:Compared with the normal control group,serum AngII levels in the model group increased?P<0.05?,TLR4,NF-?B-p65,TNF-?protein expression was significantly increased?P<0.05?,IL-10 The protein expression was significantly reduced?P<0.05?.Compared with the model group,the serum AngII levels in the rats of Dilongjiangya capsule group and benazepril group were decreased?P<0.05?,and the expression of TLR4,NF-?B-p65 and TNF-?protein in the kidney tissue were decreased?P<0.05?.The expression of IL-10 protein in the renal tissue of the middle-dose,high-dose group and benazepril group increased significantly?P<0.05?.It is suggested that Dilongjiangya capsule can regulate protein expression in TLR4/NF-?B pathway and show a certain dose-effect correlation.Conclusion:Dilongjiangya Capsule can reduce early renal damage in Spontaneously Hypertensive Rats.It's mechanism may be achieved by inhibiting the AngII-TLR4/NF-?B pathway and increasing IL-10. |
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