Renal kallikrein activation and renoprotection after dual blockade of renin-angiotensin system in diet-induced diabetic nephropathy.
OBJECTIVE
The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS) on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN).


METHODS
Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF-) β and α-smooth muscle action (SMA).


RESULTS
DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P < 0.05). Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA.


CONCLUSIONS
The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
Xia
X
Zou
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
Xiao-xi
XX
Zhang
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
Xin-yu
XY
Liu
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China ; Molecular Endocrinology and Toxicology Laboratory, Department of Biology, Hong Kong Baptist University, Kowloon 999077, Hong Kong.
Rong
R
Li
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
Min
M
Wang
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
Wei-jie
WJ
Wu
Department of Endocrinology, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510120, China.
Yi
Y
Sui
Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
Hai-lu
HL
Zhao
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D004032:Diet; D007150:Immunohistochemistry; D007249:Inflammation; D007333:Insulin Resistance; D007610:Kallikreins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose; D007610:Kallikreins; C539355:CD68 protein, rat; D000097382:CD68 Molecule