Irbesartan alleviates hepatic steatosis in db/db mice by inducing auto-phagy / 中国病理生理杂志

AIM:To investigate the effect of irbesartan on the fatty liver of db/db mice and whether autophagy is involved in the process.METHODS:Male db/db mice(n=24)were randomly divided into model group and irbesar-tan group,and 12 db/m mice with similar age and weight were selected as normal control group.After 16 weeks of inter-vention respectively,the fatty liver-related parameters including body weight, liver index, blood lipid, liver function and pathological changes in the liver were observed.The protein levels of p-PI3K,p-Akt,and p-mTOR,as well as Atg-7,bec-lin-1 and LC3B in the liver tissues were detected by Western blot,and the autophagosomes in the liver were observed under electron microscope.RESULTS:Compared with the model group,the body weight,liver index,blood lipids,alanine and aspartate aminotransferase were decreased in irbesartan group(P<0.05).Moreover,the pathological changes in the liver were significantly ameliorated in irbesartan group than that of model group.Importantly, the protein levels of p-PI3K, p-Akt and p-mTOR were decreased with irbesartan administration,while the expression of Atg-7,beclin-1 and LC3B-Ⅱwas increased(P<0.05),which resulted in a distinct increase in autophagosomes.CONCLUSION:Irbesartan alleviates he-patic steatosis in db/db mice by inhibiting the PI3K/Akt/mTOR signaling pathway and upregulating the protein expression of Atg-7,beclin-1 and LC3B-Ⅱ,thereby inducing autophagy in hepatocytes.

Effect of spinal cord extracts after spinal cord injury on proliferation of rat embryonic neural stem cells and Notch signal pathway in vitro

OBJECTIVE@#To investigate the effect of the spinal cord extracts (SCE) after spinal cord injuries (SCIs) on the proliferation of rat embryonic neural stem cells (NSCs) and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro.@*METHODS@#The experiment was conducted in 4 different mediums: NSCs+PBS (Group A-blank control group), NSCs+SCE with healthy SD rats (Group B-normal control group), NSCs+SCE with SD rats receiving sham-operation treatment (Group C-sham-operation group) and NSCs+ SCE with SCIs rats (Group D-paraplegic group). Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1, 2, 3, 4 and 5 d, respectively. The expressions of Notch1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h, respectively.@*RESULTS@#After co-culture for 1, 2, 3, 4 and 5 d respectively, the MTT values of group D were significantly higher than those of group A, group B and group C (P0.05). Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well (P0.05). There was no difference in expressions of Notch1 and Hes1 mRNA between 24 h and 48 h treatment in group D.@*CONCLUSIONS@#SCE could promote the proliferation of NSCs. It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs. Besides, SCE could increase the expression of Notch1 and Hes1 mRNA of NSC. It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs. This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene.

Effect of nitrotyrosine on renal expressions of NF-κB, MCP-1 and TGF-β1 in rats with diabetic nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of nitrotyrosine on renal expressions of nuclear factor-κB (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1) in rats with diabetic nephropathy (DN).</p><p><b>METHODS</b>Rat DN models established by a single intraperitoneal injection of streptozotocin (STZ) were randomly allocated into model group, nitrotyrosine group and ebselen group, with untreated rats as the normal control group. The rats were given the corresponding drugs for 8 weeks, and after the last administration, the 24-h urinary protein level was measured and the kidneys of the rats were harvested for detecting the protein and mRNA expressions of NF-κB, MCP-1 and TGF-β1 with immunohistochemistry and RT-PCR, respectively. The pathological changes of the kidneys were assessed microscopically.</p><p><b>RESULTS</b>Compared with those in the model group, the 24-h urinary protein level and expressions of NF-κB, MCP-1 and TGF-β1 mRNA and protein in the renal tissues were significantly increased by nitrotyrosine treatment, which also caused worsened renal pathology, while treatment with ebselen significantly ameliorated these changes.</p><p><b>CONCLUSION</b>Nitrotyrosine can up-regulate the mRNA and protein expressions of NF-κB, MCP-1 and TGF-β1 and aggravate the inflammatory reaction in the renal tissue of DN rats to promote the progression of DN.</p>

Effects of Shenkangwan on renal expressions of angiotensin II and its type I receptor in rats with early diabetic nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of Shenkangwan on the expressions of angiotensin II (AngII) and its type I receptor (AT(1)R) and the renalprotection mechanism of Shenkangwan in rats with early diabetic nephropathy (DN).</p><p><b>METHODS</b>The rat models of DN established by a single injection of streptozotocin were randomly divided into 4 groups, namely the model group, Shenkangwan treatment group, irbesartan treatment group, and Shenkangwan and irbesartan treatment group, with normal rats as the control. All the rats received daily gavage for 8 weeks. The urinary protein quality in 24 h and plasma and renal contents of AngII were measured. The expressions of AT1R at the protein and mRNA levels in the kidney tissues were measured by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. The pathological changes of the kidney were observed microscopically.</p><p><b>RESULTS</b>In DN rats, Shenkangwan reduced the urinary protein quantity in 24 h and the contents of AngII in the plasma and kidney tissues, decreased the renal expressions of AT(1)R protein and mRNA, and alleviated the morphological damage of the kidney.</p><p><b>CONCLUSIONS</b>Shenkangwan offers renalprotection against DN probably by reducing the contents of AngII in the plasma and kidney tissues and inhibiting renal AT(1)R expressions.</p>

Frequent peritoneal dialysis-related peritonitis: clinical characteristics, risk factors and treatments / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify the clinical characteristics and risk factors of frequent peritoneal dialysis (PD)-related peritonitis.</p><p><b>METHODS</b>A retrospective analysis was conducted in the peritonitis patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in our hospital. Frequent PD-related peritonitis was defined by two or more onsets in one year, and the patients with only one onset served as the control group. The clinical and laboratory data of the two groups were compared and the risk factors of PD-related peritonitis analyzed.</p><p><b>RESULTS</b>Forty-four episodes of peritonitis were recorded in the 16 patients with frequent PD-related peritonitis, as compared to 53 episodes in the 45 control patients. Compared with those in the control group, the patients with frequent peritonitis had significantly higher blood pressure (P<or=0.05) but lower hemoglobulin (P<or=0.05) and plasma albumin (P<or=0.01), with higher rates of edema (P<or=0.01), gram-negative bacteria and fungal infection (P<or=0.05) and PD catheter removal (P<or=0.05). No significant differences were found between the two groups in age, mode of catheter placement surgery, intervals between PD initiation and peritonitis occurrence, inducing factors of peritonitis, incidence of dyspnea, serum creatinin, urea, calcium, mineral phosphorus, blood or dialysate leucocytes (P>0.05). Variables identified to be associated with an increased likelihood of frequent PD-related peritonitis included hemoglobulin<70 g/L (OR=0.135, P<or=0.01) and plasma albumin<30 g/L (OR=0.181, P<or=0.05).</p><p><b>CONCLUSION</b>Compared with the patients with only one annual occurrence of peritonitis, the patients with frequent PD-related peritonitis have severer malnutrition and water overload, which are probably correlated to the high rates of PD catheter removal and poor prognosis. Severe anemia and proteinemia are risk factors and also predictive factors of frequent PD-related peritonitis. Measures to ameliorate anemia and proteinemia and effective management of celiac endogenous infection may help prevent and control frequent PD-related peritonitis.</p>

A retrospective analysis of the six-year data of peritoneal dialysis in a single center / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the epidemiology, peritoneal dialysis (PD) related complications and survival outcomes of 236 patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD) in our center from January, 2004 to November, 2009.</p><p><b>METHODS</b>The data including patient gender, age, time of PD initiation, addresses, types of medical reimbursement, primary diseases, modes of PD catheter placement surgery, types of PD catheter, PD-related complications, and time of drop out were retrospectively analyzed. PD catheter migration rate, peritonitis rate, drop out rate (DOR), length of the time of PD therapy (TOT), and survival rate were calculated and compared with those of patients in other PD centers.</p><p><b>RESULTS</b>The number of newly introduced patients increased gradually in the years from 2004 to 2009. The mean age of newly introduced patients was 47-/+16 years, and patients with age below 60 years accounted for 77.96%. Patients who paid for their own expenses accounted for 67.37% of all, and the rate of these patients decreased gradually. Similar to that in Asian-Pacific region, chronic glomerulonephritis was the most frequent cause of ESRD followed by diabetic nephropathy. The number of patients with chronic glomerulonephritis or obstructive nephropathy as the primary diseases was greater in this center than that reported in the Asian-Pacific region, accounting for 54.66% and 11.02% of all patients, respectively. In contrast, the patients with diabetic nephropathy or benign arteriolar renal sclerosis were less, accounting for 12.29% and 10.17% of all, respectively. PD catheter migration rate (8.05%) and peritonitis rate (1:44.22 patient-months) were both lower than those reported. The patient survival rates at 1, 2, 3 years were 83.65%, 51.59% and 29.81%, respectively, lower than those of other centers in the developed countries but higher than the mean levels in China. DOR decreased gradually to 11.56% in 2009, and TOT increased to 23.61 months.</p><p><b>CONCLUSION</b>The above characteristics of the patients are related to many factors, including the "PD first" principle, high prevalence of urinary calculosis in the primary source regions of most patients, preventive partial omentum resection in some patients, education and follow-up for patients, and increased expense cover by medical insurance.</p>

Effects of irbesartan on renal advanced glycation end products and their receptor in rats with early diabetic nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of irbesartan on the renal expressions of advanced glycation end products (AGEs) and their receptor (RAGEs) in rats with early diabetic nephropathy (DN) and the renoprotection mechanism of irbesartan.</p><p><b>METHODS</b>Rat DN models established by a single injection of streptozotocin were randomly divided into the model group and irbesartan treatment group. With normal rats as the control, all the rats received daily gavage for 8 weeks. The 24-h urinary protein excretion and contents of AGEs in the serum and kidney tissues were measured. The expressions of RAGEs and RAGEs protein and mRNA in the kidney tissues were detected by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. The pathological changes of the kidney were also assessed microscopically.</p><p><b>RESULTS</b>Irbesartan significantly reduced the 24-h urinary protein excretion and the contents of AGEs in the serum and kidney tissues of DN rats, resulting also in decreased expressions of RAGEs and RAGEs protein and mRNA levels in the kidney. The treatment obviously alleviated the pathological changes in the kidney of the DN rats.</p><p><b>CONCLUSION</b>Irbesartan offers renoprotection against DN possibly by reducing the serum and renal contents of AGEs and inhibiting the renal mRNA expressions of RAGEs and RAGEs.</p>

Effects of alpha-keto acid on the expression of neuropeptide Y in malnutrition rats with chronic renal failure / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of alpha-keto acid on the expression of neuropeptide Y in malnutrition rats with chronic renal failure.</p><p><b>METHODS</b>SD rats received 5/6 nephrectomy and were fed with 4% casein to establish models of malnutrition with chronic renal failure. Serum albumin, urea nitrogen, serum creatinine, type-1 insulin like growth factor and body weight of the rats were measured. The rat models were randomized into chronic renal failure group, alpha-keto acid group and normal control group, and after a 4-week treatment as indicated, neuropeptide Y mRNA levels in the hypothalamus were measured by RT-PCR in rats with surgically induced renal failure (two-stage subtotal nephrectomy). The blood neuropeptide Y of the rats were analyzed by radioimmunoassay.</p><p><b>RESULTS</b>Malnutrition occurred in chronic renal failure rats at the end of 10 weeks. Compared with those in the chronic renal failure group, the plasma neuropeptide Y concentrations in alpha-keto acid group were significantly lowered with substantially elevated neuropeptide Y mRNA expression in the hypothalamus.</p><p><b>CONCLUSION</b>alpha-keto acid capsule can improve malnutrition in rats with renal insufficiency possibly by up-regulating neuropeptide Y mRNA expression in the hypothalamus and reducing the level of blood neuropeptide Y.</p>

Protective effects of Shenkangwan against podocyte injury in rats with early diabetic nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the morphological changes and expressions of desmin and podocin in podocytes of rats with diabetic nephropathy (DN) rats and renal protection mechanism of Shenkangwan.</p><p><b>METHODS</b>DN model was established in rats by a single injection of streptozotocin. The rats were then randomly divided into model group, Shenkangwan treatment group, irbesartan treatment group, and Shenkangwan plus irbesartan treatment group, with normal rats as the control group. All the rats received daily gavage for 8 weeks. The urinary protein quantity in 24 h were detected, and the morphological changes of the kidneys were observed with optic and transmission electron microscopes. The expressions of desmin and podocin in the podocytes were detected by immunohistochemistry.</p><p><b>RESULTS</b>Shenkangwan and irbesartan reduced the urinary protein quantity in 24 h and alleviated the renal damage in DN rats, and the expression of desmin was significantly attenuated while podocin expression increased in the podocytes.</p><p><b>CONCLUSIONS</b>Shenkangwan can provide renal protection against DN in rats and alleviate the structural and functional damages of podocytes possibly by reducing desmin expression and increasing podocin expression in the podocytes.</p>

Effects of angiotensin II receptor antagonist on rat podocyte injury in early diabetic nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate nephrin and desmin expression in rat podocytes in early diabetic nephropathy (DN) and the rale of angiotensin II receptor antagonist in renal protection.</p><p><b>METHODS</b>Rat models of DN established by a injection of a single dose of streptozotocin (STZ) were randomized into model group and irbesartan group, with rats without STZ injection as the normal control group. The rats in irbesartan group were subjected to daily intragastric irbesartan administration for 8 consecutive weeks, while those in the model group received only saline in the same manner. Upon completion of the treatment, the rats were sacrificed and pathological changes of the kidney were examined with optical and transmission electron microscope. Nephrin and desmin expressions in the podocytes were detected by immunohistochemistry.</p><p><b>RESULTS</b>In rats with DN, irbesartan administration alleviated podocyte injury and significantly lowered the expression of nephrin and desmin (P<0.05).</p><p><b>CONCLUSION</b>Angiotensin II receptor antagonist may offer renal protection against DN by alleviating structural and functional podocyte damage through decreasing nephrin expression in the podocytes.</p>

Renal protective effect of Shenkang pill on diabetic rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects of Shenkang pill on renal function and extracellular matrix secretion on the diabetic rats.</p><p><b>METHOD</b>The diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ) and randomly divided into 3 groups' model control group; Capoten group and Shenkangwan group. Some normal other rats were used as normal control group. All rats were treated with corresponding drugs for 8 weeks. During and after the treatment, the general state, blood and urine glucose levels, excretion rate of the 24 hour urine protein and albumin, serum creatinine and blood urea nitrogen contents, kidney weight and relative kidney weight were measured. The mRNA of fibronectin(FN) in the kidney also detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).</p><p><b>RESULT</b>Diabetes mellitus and renal lesions occurred in the three model groups. The expression of FN mRNA of the kidney in diabetic rats increased obviously. Shenkang pill could improve the general state and renal function of the diabetic rats, decrease the blood glucose levels and the excretion rate of the 24 hour urine protein and albumin, reduce the expression of FN mRNA in kidney.</p><p><b>CONCLUSION</b>Shenkang pill has a certain protective effect on the diabetic kidney.</p>

Effect of Shenkangwan on mesangial cell NO and TGF-beta1 excretion in rats with early diabetic nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the mechanism of Shenkangwan (SKW) in treating early diabetic nephropathy (DN).</p><p><b>METHODS</b>The effect of SKW on NO and transforming growth factor (TGF)-beta(1) production by the mesangial cells (MCs) of rats with early diabetic nephropathy was evaluated with serum pharmacological method.</p><p><b>RESULTS</b>Compared with normal serum, the SKW-containing serum dose- and time-dependently inhibited TGF-beta(1) excretion and increased NO production in the MCs of rats with early DN (P<0.05 and P<0.01, respectively).</p><p><b>CONCLUSION</b>The therapeutic effect of SKW on early DN may rely on the balance modulation of cytokine network by increasing NO production and decreasing TGF-beta(1) excretion to prevent cytokine-induced damage of the MCs.</p>