Tong-xin-luo capsule inhibits left ventricular remodeling in spontaneously hypertensive rats by enhancing PPAR-gamma expression and suppressing NF-kappaB activity.
BACKGROUND
Tong-xin-luo capsule (TXL), used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, including antihypertensive effects, and is able to improve ventricular remodeling. However, the mechanisms of its action are not completely understood. The aim of this study was to evaluate the molecular mechanisms of Tong-xin-luo capsule on left ventricular remodeling in spontaneously hypertensive rats (SHR).


METHODS
Sixteen eight-week-old SHRs were randomized into an SHR group (n = 8) and a TXL group (n = 8) that were given Tong-xin-luo capsule (1.5 mg x kg(-1) x d(-1)). Eight Wistar Kyoto (WKY) rats fed with 0.9% NaCl served as the control group (WKY group). Systolic blood pressure (BP), body weight and heart rate were monitored once every two weeks. Ventricular remodeling was detected by histopathological examination. Nuclear factor kappa B P65 (NF-kappaB P65) and peroxisome proliferators activated receptor gamma (PPAR-gamma) protein and phosphorylated inhibitor kappa alpha (IkappaBalpha) protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IkappaBalpha and NF-kappaB were measured by co-immunoprecipitation. PPAR-gamma mRNA, collagen I mRNA and collagen III mRNA were measured by real-time PCR.


RESULTS
TXL inhibited NF-kappaB P65 expression and ventricular remodeling and suppressed the activation of NF-kappaB compared with the SHR group (P < 0.01, P < 0.05). TXL reduced IkappaBalpha phosphorylation, increased expression of PPAR-gamma protein and enhanced the physical interaction of the P65-P50 heterodimer with IkappaBalpha. The mRNA expression of PPAR-gamma was enhanced but the mRNA expression of collagen I mRNA and collagen I mRNA were suppressed by TXL.


CONCLUSIONS
In spontaneously hypertensive rats, TXL could inhibit ventricular remodeling induced by hypertension, and the inhibitory effect might be associated with the process of TXL increasing the expression of PPAR-gamma that could result in the inhibition of the activation of NF-kappaB.
Bu
Pei-li
PL
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health; Department of CardiologyQilu Hospital of Shandong University, Ji'nan, Shandong 250012, China.
Zhao
Xue-qiang
XQ
Wang
Li-ling
LL
Zhao
Yu-xia
YX
Li
Chuan-bao
CB
Zhang
Yun
Y
D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D047495:PPAR gamma / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D024042:Collagen Type I; D024061:Collagen Type III; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; C513941:tongxinluo