[The effects and mechanism of Tripterygium wilfordii Hook F combination with irbesartan on urinary podocyte excretion in diabetic nephropathy patients].
OBJECTIVE
To investigate the effects of the combination of tripterygium wilfordii Hook F (TwHF) and irbesartan on urinary podocyte in diabetic kidney disease (DKD) patients, and to discuss the mechanism of protective effect of TwHF on DKD.


METHODS
A total of 45 type 2 diabetic kidney disease patients were enrolled into this prospective study, and were randomly divided into 3 groups: TwHF treatment group (DT, n = 15), irbesartan treatment group (DI, n = 15), and TwHF combined with irbesartan treatment group (DTI, n = 15). After 6 weeks washout, the 3 groups were given TwHF (1-2 mg·kg⁻¹·d⁻¹), irbesartan (150-300 mg/d), and TwHF (1-2 mg·kg⁻¹·d⁻¹) combined with irbesartan (150-300 mg/d) for 12 weeks respectively. Fifteen healthy volunteers served as controls. Urinary podocytes were identified and quantitated by immunofluorescence staining of urinary sediments labeled by monoclonal antibody podocalyxin. In addition, we studied urinary connective tissue growth factor (CTGF), osteopontin (OPN) and transforming growth factor β1 (TGFβ1) concentrations in DKD patients by enzyme-linked immunosorbent assay.


RESULTS
Urinary detached podocytes were obviously higher in the urine of DKD patients than in healthy controls (P < 0.01). Podocyte detection rate was 86.6% in the urine of DKD patients. The protein expressions of CTGF, OPN and TGFβ1 in patients with urinary podocyte were significantly increased than those without urinary podocyte (P < 0.05 or 0.01).Correlation analysis showed that there was positive correlation between urinary protein excretion and urinary podocytes (r = 0.79, P < 0.01) and there were positive correlations between the number of urinary podocytes and urinary protein expressions of CTGF, OPN and TGFβ₁ (r = 0.56, 0.41, 0.44, respectively, all P values <0.01). Urinary albumin excretion and urinary podocytes were significantly decreased in all treatment groups (P < 0.01), simultaneously, urinary concentrations of CTGF, OPN and TGFβ₁ were reduced in all groups at week 12 after intervention of TwHF, irbesartan and TwHF combined with irbesartan(P < 0.01), and these changes were more distinguished in combined treatment group (P < 0.05).


CONCLUSIONS
Urinary podocyte in the urine may be suggested to be an early effective marker of disease activity in DKD. TwHF may be effective to prevent podocyte injury in DKD, which may be mediated, at least partly, by down-regulating the expression of CTGF, OPN and TGFβ₁. There is a synergistic protective effect of TwHF combined with irbesartan on podocyte injury in DKD patients.
Department of Nephrology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao 266002, China (Email:anita1685@163.com).
Rui-xia
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Ma
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Zhao
Wei
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Zhang
D000368:Aged; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000652:urine; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000652:urine; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D011446:Prospective Studies; D013777:Tetrazoles / Q000494:pharmacology*; D029757:Tripterygium / Q000737:chemistry*
D001713:Biphenyl Compounds; D004365:Drugs, Chinese Herbal; D013777:Tetrazoles; D000077405:Irbesartan